interleukin-8 and Acute-Disease

Urinary tract infection (UTI) is common among pediatric population. Pyelonephritis, especially in young infants, is associated with a significant morbidity. Usually, clinical manifestations, laboratory findings, and imaging are used to differentiate between lower and upper UTI. Lack of specific clinical findings and commonly used nonspecific blood indices are important hamper differentiation between lower and upper UTI in early stages. Imaging techniques are neither cost benefit nor safe for detection of UTI. Recent efforts have focused on characterization of novel serum and urinary biomarkers for early detection of acute pyelonephritis in children. It seems that urinary NGAL, NAG, TNF-α and IL-8 may be used as novel markers for early diagnosis of acute pyelonephritis in children.

Topics: Acute Disease; beta-N-Acetyl-Galactosaminidase; Biomarkers; Child; Child, Preschool; Early Diagnosis; Humans; Infant; Interleukin-8; Lipocalin-2; Pyelonephritis; Tumor Necrosis Factor-alpha; Urinary Tract Infections

Several studies have been performed to investigate the associations between interleukin (IL)-8 rs4073 polymorphism and acute pancreatitis (AP), but the results are inconclusive. We conducted this cumulative meta-analysis for a precise estimate of the relationship between IL-8 rs4073 polymorphism and acute pancreatitis.. We searched the electronic databases for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. For a better presentation of how the pooled ORs changed as updated evidence accumulated, we used forest plots from a cumulative meta-analysis method.. Ten studies involving 1646 AP patients and 1816 controls were finally included in this meta-analysis. Cumulative meta-analyses indicated there is a consistent trend toward association after the initial discovery. Under the allelic, dominant, recessive and homozygous models, the pooled ORs were 1.265 (1.147-1.395, p < 0.001), 1.304 (1.127-1.508, p < 0.001), 1.431 (1.203-1.702, p < 0.001), and 1.634 (1.334-2.001, p < 0.001), respectively.. This meta-analysis demonstrated a suggestive result that people who carried the risk A allele of the IL-8 rs4073 polymorphism may be more sensitive to acute pancreatitis.

Topics: Acute Disease; Alleles; Databases, Factual; Genetic Predisposition to Disease; Humans; Interleukin-8; Odds Ratio; Pancreatitis; Polymorphism, Single Nucleotide

Type B acute aortic dissection (AAD) spares the ascending aorta and is optimally managed by medical therapy in the absence of complications. However, patients with enhanced inflammation sometimes present with aortic enlargement, thereby facing undesirable outcomes. Thus, a better understanding of the molecular and cellular mechanisms involved in AAD-associated inflammatory processes and the requirement for a novel therapeutic approach for patients with type B AAD are unmet clinical needs. This study showed that dissection per se induced neutrophil-chemoattractant chemokine expression in the aortic tunica adventitia, possibly by mechanical injury and stretching followed by pseudolumen formation. Subsequent systemic changes in chemokine-dependent signaling caused neutrophilia and massive neutrophil accumulation in the dissected aorta, thereby leading to aortic enlargement and rupture via interleukin-6 production. Importantly, temporal and spatial dynamics of inflammatory cytokine and chemokine elevation, as well as leukocyte recruitment, were consistent between rodents and humans. Our study provides a new mechanistic insight into neutrophil-mediated adventitial inflammation after AAD and implicates CXCR2- or interleukin-6 neutralization as novel therapeutic strategies to prevent large-artery complications, including aneurysm formation and rupture, in patients with type B AAD.

Topics: Acute Disease; Angiotensin II; Animals; Aorta; Aortic Aneurysm; Aortic Dissection; Chemokines; Gene Expression; Humans; Immune System Diseases; Interleukin-6; Interleukin-8; Leukocyte Disorders; Mice; Molecular Targeted Therapy; Neutrophils; Receptors, Interleukin-8B; Systemic Inflammatory Response Syndrome

Circumstantial evidence exists that certain neutrophilic inflammatory processes are regulated by T cells, but how this occurs is not well understood. The present review presents data on how T cells may directly orchestrate a neutrophilic inflammation by specific release of the neutrophil-attracting chemokine CXCL8 (formerly known as interleukin-8).. Acute generalized exanthematous pustulosis (AGEP) is an uncommon cutaneous eruption that is most often provoked by drugs, by acute infections with enteroviruses, or by mercury. It is characterized by acute, extensive formation of nonfollicular sterile pustules on an erythematous background, fever and elevated numbers of blood neutrophils. Involvement of T cells in drug-induced AGEP was suggested by positive patch tests and lymphocyte transformation tests. Moreover, drug-specific CD4+ and CD8+ T cells could be isolated and propagated in vitro from patch test sites and blood from AGEP patients. Their main characteristic is a high level of CXCL8 production.. T cells are involved even in some neutrophil-rich inflammatory responses, and they may orchestrate the immune reaction directly by high CXCL8 production or indirectly via interleukin-17 production, which induces CXCL8 production in various cell types. AGEP serves as a valuable model for characterizing T cells with a particular function--namely production of CXCL8--leading to neutrophilic inflammation. It is tempting to speculate that elucidation of this pathomechanism will help to improve our understanding of similar neutrophilic eruptions (e.g. pustular psoriasis) and may reveal new targets for pharmacotherapeutic interventions in such diseases.

Topics: Acute Disease; Drug Eruptions; Exanthema; Humans; Inflammation; Interleukin-8; Neutrophils; T-Lymphocytes

The clinical manifestations of acute pancreatitis (AP) vary significantly from mild to lethal in form, the severity of the disease being largely determined by the actions of various kinds of inflammatory mediators, including cytokines, reactive oxygen species, proteolytic enzymes, and lipids, as well as gaseous mediators. Despite increasing knowledge implicating the involvement of cytokines in the progression of AP, no clinical trials pertaining to cytokine modulation have been performed so far. Progress in intensive care technologies has contributed to the improvement of mortality and morbidity rates in severe AP in the past decade; however, it appears to be reasonable for clinicians to "line up their sights" on the modulation of cytokines as a direct treatment. In contrast to the large body of experimental studies demonstrating the beneficial effects of cytokine modulation on the amelioration of the disease, direct extrapolation from these successful experiments to the clinical situation seems to be extremely difficult.

Topics: Acute Disease; Animals; Biomarkers; Chemokines; Cytokines; Humans; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Mice; Pancreatitis; Predictive Value of Tests; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Tumor Necrosis Factor-alpha

Human parvovirus B19 infection is occasionally associated with acute lymphocytic myocarditis (ALM). Three infants with B19 virus-associated ALM were followed up clinically, histologically, and immunovirologically. Each infant had B19 virus DNA in the blood or B19 virus-specific IgM antibodies. Two infants with postnatal infection recovered after immunosuppressive therapy. The third infant with possible prenatal infection developed chronic persistent myocarditis associated with persistent B19 virus DNA in the blood. All 3 infants had increased levels of interferon-gamma, tumor necrosis factor-alpha, and interleukins -6 and -8. Four newborns with congenital B19 virus infection and 4 infants and children who had postnatally acquired B19 virus infection without myocarditis all had normal levels of these cytokines. These observations suggest that B19 virus infection in infancy causes ALM in some infants and children.

Topics: Acute Disease; Antibodies, Viral; Chronic Disease; Cytokines; DNA, Viral; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Infant; Interferon-gamma; Interleukin-6; Interleukin-8; Myocarditis; Parvoviridae Infections; Parvovirus B19, Human; Tumor Necrosis Factor-alpha

The central, detrimental role of the inflammatory cytokines IL-1 and TNF and the biologically active phospholipid PAF in the pathogenesis of AP has been established over the past 8 years. A number of antagonists to these mediators have been used successfully in the laboratory setting and are currently being examined in prospective randomized trials. The effectiveness of any antagonist depends not only on its ability to block the effects of the inflammatory mediators but also on its administration early enough in the course of the pancreatitis before pancreatic necrosis or organ dysfunction.

Topics: Acute Disease; Animals; Cytokines; Humans; Inflammation Mediators; Interleukin-1; Interleukin-6; Interleukin-8; Pancreatitis; Platelet Activating Factor; Tumor Necrosis Factor-alpha

Apart from ventilatory and bacteriologic aspects, understanding the pathomechanisms of inflammation in chronic sinusitis and nasal polyposis seems crucial for further success in disease treatment. New insights into inflammatory processes became recently possible by investigating the pattern of cytokines and chemokines as well as adhesion molecules in different acute and chronic sinus diseases. The proinflammatory cytokines interleukin (IL)-1 beta, IL-6 and especially the neutrophil-chemoattractant IL-8 play a dominant role in acute sinusitis, as was shown before for viral and allergic rhinitis. In contrast, IL-3 protein dominates the cytokine profile in chronic sinusitis, giving support to a variety of inflammatory cells. The most striking finding was the increased synthesis of IL-5 protein in bilateral nasal polyposis, whereas IL-5 was not found in controls or antrochoanal polyps. As this cytokine is known to enhance eosinophil activation and survival, our data point to IL-5 as a key protein in the pathomechanism of tissue eosinophilia in nasal polyposis. The investigation of cytokine patterns may furthermore help to differentiate between sinusitis subgroups, e.g. in the classification of sinus diseases.

Topics: Acute Disease; Cell Adhesion Molecules; Chemokines; Chemotaxis, Leukocyte; Chronic Disease; Cytokines; Eosinophilia; Eosinophils; Humans; Interleukin-1; Interleukin-3; Interleukin-5; Interleukin-6; Interleukin-8; Maxillary Sinus; Nasal Polyps; Neutrophils; Paranasal Sinus Neoplasms; Polyps; Rhinitis; Sinusitis

Severe, acute pancreatitis is commonly associated with a systemic illness which may result in multiple organ failure. There is evidence that an aberrant immune response, involving increased secretion of proinflammatory cytokines from activated monocytes and mononuclear phagocytes, is responsible for another systemic illness--septic shock. Previous studies have investigated whether there is a correlation between plasma cytokine levels and severity of pancreatitis. However, these results may not reflect mononuclear phagocyte activation. In this paper, monocytes (collected from patients with severe pancreatitis) were cultured in vitro and secreted cytokine levels measured after 24 hours by ELISA. Secretion of tumour necrosis factor alpha, interleukin-6 and interleukin-8 was higher in cells taken from patients who later developed systemic complications. There was no difference in the secretion of interleukin-1 beta. The mechanism by which mononuclear phagocytes are activated in acute pancreatitis, and the role of genetic predisposition, are discussed.

Topics: Acute Disease; Causality; Cytokines; Endotoxins; HLA Antigens; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Monocytes; Mononuclear Phagocyte System; Pancreatitis; Phagocytes; Tumor Necrosis Factor-alpha

Cytokines are important immunoregulatory mediators. Their contribution to the pathogenesis of acute and chronic gastroenterological disorders is obvious. Increased expression of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) can be detected in inflammatory bowel disease. During the last few years it has also been recognized that activated leukocytes have an important role in the multisystem involvement of acute pancreatitis. Activation of leukocytes is an early event during severe acute pancreatitis, and it may be a pathogenetic factor in the severity of the disease. The review summarizes the recent findings in the field of inflammatory cytokines with particular attention of TNF, IL-1, IL-6, and IL-8 during severe acute pancreatitis and underscores the role of the activated leukocytes in the pathogenesis of complicated acute pancreatitis.

Topics: Acute Disease; Adjuvants, Immunologic; Cytokines; Humans; Inflammation Mediators; Inflammatory Bowel Diseases; Interleukin-1; Interleukin-6; Interleukin-8; Pancreatitis; Severity of Illness Index; Tumor Necrosis Factor-alpha

Severe acute pancreatitis (SAP) is a highly morbid condition in general population as well as in solid organ transplant (SOT) recipients. The present study aimed to investigate the effect of continuous renal replacement therapy (CRRT) with different anticoagulation methods on the expression levels of cytokines in SAP.. A total of 120 patients with SAP, admitted into our hospital between September 2017 and July 2020, were enrolled as the research subjects and randomly divided into a control group (60 cases) and a study group (60 cases). CRRT with low molecular weight (LMW) heparin‑calcium anticoagulation was conducted on patients in the control group, and CRRT with topical citrate + low-dose LMW heparin‑calcium anticoagulation was conducted on patients in the study group. The expressions of cytokines in the two groups were compared after treatment.. There was no significant difference in white blood cells (WBC), C-reactive proteins (CRP), and procalcitonin (PCT) before treatment between the two groups (P > 0.05). After treatment, the levels of WBC (P = 0.006), CRP (P < 0.001), and PCT (P < 0.001) were significantly lower in the study group when compared with those in the control group. There was no significant difference in the concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) between the two groups before treatment (P > 0.05). After treatment, the concentrations of IL-6, IL-8, and TNF-α were significantly lower in the study group when compared with those in the control group. The APACHEII, SOFA and Ranson scores of the two groups were analyzed, and there was no difference between the two groups before treatment (P > 0.05). After treatment, the score of the study group was lower than that of the control group (P < 0.05).. CRRT with topical citrate + low-dose LMW heparin‑calcium anticoagulation in the treatment of patients with SAP reduces the levels of WBC, CRP, and PCT and the concentrations of cytokines, including IL-6, IL-8, and TNF-α. This inhibits the release of inflammatory mediators in patients with SAP and reduces damage to the body caused by the inflammatory response, thus effectively improving the patients' condition.

Topics: Acute Disease; Anticoagulants; C-Reactive Protein; Citrates; Continuous Renal Replacement Therapy; Cytokines; Humans; Interleukin-6; Interleukin-8; Pancreatitis; Renal Replacement Therapy; Tumor Necrosis Factor-alpha

One of the most serious complications of acute febrilepyelonephritis in children is the development of renal scar. Thisstudy aimed to investigate the effect of dexamethasone on urinarycytokine levels and renal scar in children with acute pyelonephritis.. In a double-blind randomized clinical trial, 60 childrenaged 3 months to 12 years with acute febrile pyelonephritis enrolled.The experimental group was treated with a combination of antibioticand dexamethasone, and the control group underwent treatmentwith antibiotic and placebo. The urinary levels of interleukin -6(UIL-6) and -8 (UIL-8) were measured before treatment as baselineand were repeated four days later.. 52 cases (23 patients with mean age of 34.19 ± 30.82 monthsin the dexamethasone group, and 29 patients with mean age of50.55 ± 44.41 months in the control group) completed the study. Inthe control group, the UIL-6 and UIL-8 level became significantlylower after four days treatment (P < .05). In the dexamethasonegroup, there was a statistically significant difference between bothUIL-6 and UIL-8 levels before and after treatment (P < .05). Inpatients who had scar on DMSA scan, the mean UIL-8 and UIL-6levels were significantly high before and after treatment.. Results of this study showed that dexamethasone plusantibiotic have no clear superiority to antibiotic therapy alone indecreasing inflammatory cytokines and scar formation. We foundout that patients with scar had sustained high levels of biomarkersbefore and after treatment.

Topics: Acute Disease; Child; Child, Preschool; Cicatrix; Cytokines; Dexamethasone; Double-Blind Method; Female; Humans; Infant; Interleukin-6; Interleukin-8; Kidney; Male; Pyelonephritis; Radionuclide Imaging

To investigate the efficacy of percutaneous catheter drainage (PCD) and peritoneal dialysis (PD) in the treatment of severe acute pancreatitis (SAP) and its underlying mechanism.. Totally 64 SAP patients were included in our study and randomly assigned into PCD+PD group (the combination group, N.=32) and convention group (N.=32). SAP patients in the combination group were treated with percutaneous catheter drainage combined with peritoneal dialysis, while those in the convention group were treated with conventional method. The treatment efficacy of both methods were evaluated by comparing levels of plasma inflammatory cytokines (IL-6, IL-8, TNF-α, C-reactive protein, procalcitonin and leukocyte count), relative indexes of important organs (aspartate aminotransferase, alanine aminotransferase, creatinine and urea nitrogen) and other clinical data (amelioration time of abdominal pain and abdominal distension, Balthazar CT scores, acute physiology and chronic health enquiry II score, length of hospital stay, complications and prognosis).. The expression levels of inflammatory cytokines were significantly decreased in the combination group in a time-dependent manner in comparison with those of the convention group. In addition, the amelioration time of abdominal pain and abdominal distension, length of hospital stay, Balthazar CT scores and the acute physiology and chronic health care II scores in the combination group were also significantly decreased in comparison with those of the convention group.. The combination treatment of PCD and PD effectively relieves the clinical symptoms of SAP by clearing plasma inflammatory cytokines.

Topics: Abdominal Pain; Acute Disease; Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Blood Urea Nitrogen; C-Reactive Protein; Combined Modality Therapy; Creatinine; Drainage; Female; Humans; Interleukin-6; Interleukin-8; Length of Stay; Leukocyte Count; Male; Middle Aged; Pancreatitis; Peritoneal Dialysis; Procalcitonin; Prognosis; Prospective Studies; Tumor Necrosis Factor-alpha

To evaluate the effect of proton pump inhibitors (PPIs) therapy on severe acute pancreatitis (SAP) patients.. No significant difference was found in CRP,IL-6,IL-8,TNF-α and PCT between the two groups (. PPIs therapy did not show benefit on alleviating systemic inflammatory response and clinical scores in SAP patients,and didn't improve the prevention of peptic ulcer and gastrointestinal hemorrhage.

Topics: Acute Disease; C-Reactive Protein; Calcitonin; Esomeprazole; Humans; Interleukin-6; Interleukin-8; Pancreatitis; Prospective Studies; Proton Pump Inhibitors; Tumor Necrosis Factor-alpha

To assess the effects of the cyclooxygenase-1/cyclooxygenase-2 inhibitor lornoxicam on systemic complications in patients with acute pancreatitis, Toll-like receptor (TLR)2 and TLR4 messenger RNA expression, and cytokine secretion (IL-6, IL-8, tumor necrosis factor-α).. Adult patients with acute pancreatitis were randomized to standard therapy or standard therapy plus lornoxicam. Standard therapy included analgesics, spasmolytics, octreotide, pantoprazole, and intravenous fluids. The TLR2 and TLR4 expression levels and TLR2- and TLR4-mediated cytokine production in peripheral blood mononuclear cells were assessed in patients with severe complications and in healthy volunteers (n = 15).. A total of 334 patients received standard therapy (n = 246) or standard therapy plus lornoxicam (n = 88), 172 (51.5%) of whom developed systemic complications. Occurrence of complications was higher with standard therapy compared with lornoxicam (57.3% versus 35.2%; P = 0.00034), as was mortality (19.1% versus 6.8%; P = 0.006). The TLR2 and TLR4 expression and TLR2 and TLR4-mediated cytokine production were significantly higher in patients with systemic complications of acute pancreatitis compared with healthy volunteers. Relative TLR2 expression and cytokine production were significantly reduced in patients receiving lornoxicam versus standard therapy.. The use of lornoxicam at the onset of acute pancreatitis decreased TLR2 and TLR4 expression and the production of proinflammatory cytokines, thereby reducing the risk of systemic complications and mortality.

Topics: Acute Disease; Adult; Aged; Biomarkers; Cyclooxygenase Inhibitors; Female; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Pancreatitis; Piroxicam; Prospective Studies; RNA, Messenger; Russia; Time Factors; Toll-Like Receptor 2; Toll-Like Receptor 4; Treatment Outcome; Tumor Necrosis Factor-alpha

In acute pancreatitis (AP) tumor necrosis factor-α mediates multi-organ failure; in animal models its blockade with pentoxifylline ameliorates AP. The efficacy of pentoxifylline in predicted severe AP (pSAP) was tested in a double-blinded, randomized, control trial. Twenty-eight patients with pSAP were randomized within 72 hours of diagnosis to pentoxifylline or placebo. Baseline characteristics were similar in both groups. The pentoxifylline group had fewer intensive care unit admissions and shorter intensive care unit and hospital stays of longer than 4 days (all P < .05). Patients receiving pentoxifylline had no adverse effects. Pentoxifylline within 72 hours of pSAP is safe; a larger study of pentoxifylline in AP is needed to confirm efficacy. ClinicalTrials.gov number: NCT01292005.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Double-Blind Method; Female; Humans; Interleukin-6; Interleukin-8; Length of Stay; Male; Middle Aged; Pancreatitis; Pentoxifylline; Phosphodiesterase Inhibitors; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult

This study aimed to address whether hydroxyethyl starch (HES) is beneficial for intra-abdominal pressure (IAP) in severe acute pancreatitis (SAP) in early stages.. Forty-one patients with SAP were randomized to HES group (n = 20) and the Ringer's lactate (RL) group (n = 21). The groups received 6% HES 130/0.4 for 8 days and RL solution without colloid, respectively. The primary end point was the IAP. The secondary end points were fluid balance, major organ complications, the Acute Physiology and Chronic Heath Evaluation II score, and the serum levels of C-reactive protein, interleukin-6, and interleukin-8.. The characteristics of baseline data were similar in the 2 groups. In the HES group, the IAP was significantly lower in 2 to 7 days, and fewer patients received mechanical ventilation (15.0% vs 47.6%). A negative fluid balance was observed earlier in the HES group than in the RL group (2.5 ± 2.2 vs 4.0 ± 2.5 days).. Fluid resuscitation with HES in the early stages of SAP can decrease the risk of intra-abdominal hypertension and reduce the use of mechanical ventilation.

Topics: Acute Disease; Adult; C-Reactive Protein; Female; Fluid Therapy; Humans; Hydroxyethyl Starch Derivatives; Interleukin-6; Interleukin-8; Intra-Abdominal Hypertension; Male; Middle Aged; Pancreatitis; Plasma Substitutes; Resuscitation; Severity of Illness Index; Treatment Outcome

Our aim was to study the therapeutic effects and the mechanism of combination of hemofiltration (HF) and peritoneal dialysis (PD) in the treatment of severe acute pancreatitis (SAP).. Fifty-one cases of SAP were randomly divided into the HF+PD group (treated group, 36 patients) and the non-HF+PD group (control group, 15 patients). Both groups were treated by the same traditional methods. The relief time of abdominal pain and abdominal distension, computed tomographic scores, acute physiology and chronic health enquiry II scores, length of stay, cost of hospitalization, operability, and recovery rate of the 2 groups were compared. The concentration of tumor necrosis factor-alpha, IL-6, and IL-8 in serum and ascites volumes was determined before and after treatment.. : The mean time of abdominal pain relief, amelioration of abdominal distension, decrease of computed tomographic scores, acute physiology and chronic health enquiry II scores, the mean length of stay, and cost of hospitalization of the treated group were significantly shorter or less than those of the control group. The aforementioned inflammatory cytokines, detected at the end of 1 day and 2 days after HF+PD treatment, were decreased significantly compared with those observed in pretherapy and the control group.. Inflammatory cytokines, which overproduced in SAP, can be eliminated effectively from the blood and the ascites by HF+PD treatment.

Topics: Acute Disease; Adult; Aged; APACHE; Combined Modality Therapy; Hemofiltration; Humans; Interleukin-6; Interleukin-8; Length of Stay; Middle Aged; Pancreatitis; Peritoneal Dialysis; Treatment Outcome; Tumor Necrosis Factor-alpha

Acute respiratory failure in neonates (e.g. ARDS, meconium aspiration pneumonitis, pneumonia) is characterized by an excessive inflammatory response, governing the migration of polymorpho-nuclear leukocytes (PMNLs) into lung tissue and causing consecutive impairment of gas exchange and lung function. Critical to this inflammatory response is the activation of nuclear factor-kappaB (NF-kappaB) that is required for transcription of the genes for many pro-inflammatory mediators. We asked whether the inhibition of NF-kappaB activity using either a selective inhibitor (IKK-NBD peptide) or dexamethasone would be more effective in decreasing NF-kappaB activity and chemokine expression in pulmonary cells. Changes in lung function were repeatedly assessed for 24h following induction of acute respiratory failure and therapeutic intervention. We conducted a randomized, controlled, prospective animal study with mechanically ventilated newborn piglets which underwent repeated airway lavage (20+/-2 [SEM]) to remove surfactant and to induce lung inflammation. Admixed to 100 mg kg(-1) surfactant, piglets then received either IKK-NBD peptide (S+IKK), a selective inhibitor of NF-kappaB activation, its control peptide without intrinsic activity, dexamethasone (S+Dexa), its solvent aqua, or an air bolus only (all groups n=8). After 24h of mechanical ventilation, the following differences were measured: PaO(2)/FiO(2) (S+IKK 230+/-9 mm Hg vs. S+Dexa 188+/-14, p<0.05); ventilation efficiency index (0.18+/-0.01 [3800/(PIP-PEEP)(*)f(*)PaCO(2)] vs. 0.14+/-0.01, p<0.05); extravascular lung water (24+/-1 ml kg(-1) vs. 29+/-2, p<0.05); PMNL in BAL fluid (112+/-21 cells microl(-1) vs. 208+/-34, p<0.05), IL-8 (351+/-117 pg ml(-1) vs. 491+/-144, p=ns) and leukotriene B(4) (23+/-7 pg ml(-1) vs. 71+/-11, p<0.01) in BAL fluid. NF-kappaB activity in the nucleus of pulmonary cells differed by 32+/-5% vs. 55+/-3, p<0.001. Differences between these two intervention groups were more pronounced in the second half of the observation period (hours 12-24). At 24h of mechanical ventilation, inhibition of NF-kappaB activity by IKK-NBD peptide admixed to surfactant as a carrier caused improved gas exchange, lung function and reduced pulmonary inflammation, as evidenced by reduction in PMNL migration into lung tissue due to reduced nuclear NF-kappaB activity. We conclude that IKK-NBD admixture to surfactant in acute neonatal respiratory failure is superior to dexamethasone administration within the fir

Topics: Acute Disease; Animals; Animals, Newborn; Anti-Inflammatory Agents; Blood Cell Count; Bronchoalveolar Lavage Fluid; Dexamethasone; Inflammation; Interleukin-8; Leukotriene B4; Lung Diseases; Neutrophils; NF-kappa B; Organ Size; Pulmonary Gas Exchange; Pulmonary Surfactants; Respiration, Artificial; Respiratory Tract Diseases; Swine

The currently used National Cancer Institute (NCI) adverse events criteria for mucosal barrier injury (MBI) are insufficient for use in children. We searched for objective, easily measurable indicators for MBI in children with cancer.. In children with acute myeloid leukemia, various MBI-related clinical and laboratory tests were investigated, reflecting clinical severity (NCI symptomatic adverse events criteria (gold standard), daily gut score (DGS)), inflammation (plasma and fecal interleukin-8 (IL-8), fecal calprotectin), enterocytic loss (plasma citrulline, ratio fecal human DNA/total DNA) and intestinal permeability (sugar absorption tests).. Intestinal MBI as detected by the NCI adverse events criteria was found in 55% of chemotherapy cycles, correlating well with the continuous DGS (n = 55, rho = 0.581; P < 0.001). Intestinal cell loss as measured by the ratio fecal human DNA/total DNA and plasma citrulline correlated well with both NCI criteria (n = 61, rho = 0.357, P = 0.005 resp. n = 58, rho = -0.482; P < 0.001) and DGS (n = 54, rho = 0.352, P = 0.009 resp. n = 55, rho = -0.625; P < 0.001). Plasma IL-8 correlated strongly to plasma citrulline (n = 46, rho = -0.627; P < 0.001).. MBI was reflected by parameters indicating inflammation (IL-8) and cell loss (plasma citrulline, ratio fecal human DNA/total DNA). We conclude that plasma citrulline might be a good parameter for MBI. Further studies are needed to show whether plasma citrulline can be used as a marker for MBI in future research.

Topics: Acute Disease; Adolescent; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Carbohydrates; Cell Death; Child; Child, Preschool; Citrulline; Cytarabine; Daunorubicin; DNA; Enterocytes; Etoposide; Feces; Female; Humans; Infant; Interleukin-8; Intestinal Absorption; Leukemia, Myeloid; Leukocyte L1 Antigen Complex; Male; Mitoxantrone; Models, Biological; Mucositis; Stomatitis

We evaluated the effect of sivelestat sodium (SiV), a novel synthesized polymorphonuclear (PMN) elastase inhibitor, on acute lung injury (ALI) caused by cardiopulmonary bypass (CPB).. Fourteen patients who underwent cardiopulmonary surgery using CPB, followed by the development of both systemic inflammatory response syndrome (SIRS) and ALI, were treated with either 0.2 mg/kg per hour SiV (SiV group, n = 7) or saline (control group, n = 7) for 4 days from the time of arrival in the intensive care unit.. The SiV group had a significantly lower ratio of serum PMN elastase and interleukin (IL)-8, a significantly lower ratio of the respiratory index, and a significantly higher ratio of PaO(2)/FiO(2) after 24 h of treatment than the control group.. Sivelestat sodium suppressed the production of PMN elastase and IL-8, resulting in improved respiratory function in patients with ALI caused by CPB.

Topics: Acute Disease; Aged; Cardiopulmonary Bypass; Female; Glycine; Humans; Interleukin-8; Leukocyte Elastase; Male; Middle Aged; Perfusion; Respiratory Distress Syndrome; Serine Proteinase Inhibitors; Sulfonamides; Systemic Inflammatory Response Syndrome

Sivelestat sodium hydrate (sivelestat) is a selective inhibitor of polymorphonuclear leukocyte elastase (PMN-E). We administered sivelestat to patients with septic acute lung injury (ALI) to examine its usefulness. The primary endpoints in the study were the duration of artificial ventilation and pulmonary oxygenation ability, and the secondary endpoints were mortality and the concentrations of PMN-E, SP-D, TNF-alpha and IL-8 in blood. In the sivelestat group, the duration of artificial ventilation, pulmonary oxygenation ability, and the blood PMN-E, SP-D, TNF-alpha and IL-8 concentrations decreased significantly. Administration of sivelestat was found to reduce alveolar dysfunction and improve respiratory function, and it was suggested that early administration might be useful.

Topics: Acute Disease; Adolescent; Adult; Aged; Glycine; Humans; Interleukin-8; Leukocyte Elastase; Leukocytes; Middle Aged; Oxygen; Pulmonary Circulation; Pulmonary Surfactant-Associated Protein D; Respiration, Artificial; Serine Proteinase Inhibitors; Sulfonamides; Survival Analysis; Systemic Inflammatory Response Syndrome; Treatment Outcome; Tumor Necrosis Factor-alpha

To study the therapeutic effects and its mechanism of combination of hemofiltration (HF) and peritoneal dialysis (PD) in the treatment of severe acute pancreatitis (SAP).. Forty patients with SAP were divided at random into the HF + PD group (therapeutic group, 25 patients) and the non-HF + PD group (contrast group, 15 patients). Both groups were treated by the conventional mode of therapy. The release time of abdominal pain and distention, CT scores, APACHE II scores, the time of hospital stay, cost of treatment in hospital, operative rate and rate of complications and recovered rate of the two groups were compared. Simultaneously, the concentration of serum and fluid filtrated pro-inflammatory cytokines TNF, IL-6 and IL-8 were also determined pro and post the therapy.. The time needed for the disappearance of abdominal pain and the amelioration of abdominal distension, CT scores, APACHE II scores, the average hospital stay and hospital cost of the therapeutic group were significantly decreased compared with those of the contrast group. The cytokines detected at the end of 1d, 2d after HF + PD were decreased significantly compared with those observed in pro HF + PD and the contrast group.. The above results show that the cytokines overproduced during the development of SAP can be removed effectively from the circulation and the fluid filtrated by means of HF + PD. The continual deterioration of the local focus and systemtic presentation could be prevented effectively too, and the earlier the treatment of HF + PD, the better the prognosis.

Topics: Acute Disease; Combined Modality Therapy; Female; Hemofiltration; Humans; Interleukin-6; Interleukin-8; Length of Stay; Male; Pancreatitis; Peritoneal Dialysis; Treatment Outcome; Tumor Necrosis Factor-alpha

Glutamine is an important fuel for rapidly dividing cells such as enterocytes and lymphocytes. Exogenous glutamine supplementation in catabolic states preserves intestinal mucosal structure and function, decreases bacterial translocation, and supports normal immunologic responses. This study was planned to assess the effect of glutamine supplementation on duration and severity of diarrhea and to assess its immunomodulatory effect by measuring serum interleukin-8 (IL-8) and salivary immunoglobulin A (sIgA) in children with acute diarrhea.. In this placebo-controlled, double-blind and randomized trial, 6- to 24-month-old otherwise healthy children admitted to the Diarrheal Diseases Training and Treatment Center with acute diarrhea received either 0.3 g/kg/day of glutamine (n = 63) or placebo (n = 65) for 7 days. Serum IL-8 and sIgA levels were determined on admission and 7 days later. All cases were followed until the diarrheal episode ended. Anthropometric measurements and history of subsequent infectious diseases were monitored monthly for 3 months after treatment.. Mean duration of diarrhea in the glutamine treated group was significantly shorter than that of the placebo group (3.40 +/- 1.96 days, 4.57 +/- 2.48 days, respectively; P = 0.004). No differences in serum IL-8 and sIgA were found between groups on admission or 1 week later. During 3 month follow-up, mean weight gain and incidence of infectious diseases were similar in both groups.. Duration of diarrhea was shorter in children supplemented with glutamine. The beneficial impact of glutamine supplementation seems to be through effects on gastrointestinal mucosa rather than the host immune response.

Topics: Acute Disease; Diarrhea; Dietary Supplements; Double-Blind Method; Female; Glutamine; Humans; Immunoglobulin A, Secretory; Infant; Interleukin-8; Male; Saliva; Treatment Outcome

Given its role in mediating inflammation, the use of urinary interleukin-8 (IL-8) was assessed in the non-invasive diagnosis of acute and chronic inflammatory diseases.. IL-8 was measured by an enzyme linked immunosorbent assay in random urine samples (1 ml each) carrying code numbers and taken from 208 patients: 177 adults and 31 children presenting with a range of active or inactive inflammatory conditions.. In the appropriate controls and in patients with inactive inflammation, the median urinary IL-8 levels ranged from 7-12 pg/ml, compared with 104 pg/ml in active ulcerative colitis (p = 0.002), 54 in active Crohn's disease (p = 0.025), 93 in active rheumatoid arthritis (p = 0.001), 107 in acute cholecystitis (p<0.0001), 127 in acute appendicitis (p = 0.0001), and 548 pg/ml in urinary tract infection (p<0.0001). Children with non-viral inflammation/infection also had higher IL-8 values (median, 199 pg/ml; p = 0.0001) than those with viral infection (median, 7 pg/ml) or non-specific conditions (median, 10 pg/ml). In the study group as a whole urinary IL-8 values correlated positively with peripheral blood white cell count (r = 0.32; p < 0.001), erythrocyte sedimentation rate (r = 0.41; p<0.001), and C-reactive protein (r = 0.33; p<0.001).. Taking the appropriate clinical situation into account, urinary IL-8 measurement helps in the non-invasive assessment of active inflammation in at least a number of common acute and chronic conditions.

Topics: Acute Disease; Adult; Biomarkers; C-Reactive Protein; Child; Chronic Disease; Humans; Inflammation; Interleukin-8; Leukocyte Count; Multivariate Analysis; Sensitivity and Specificity

Platelet activating factor (PAF) is believed to amplify the activity of key mediators of the systemic inflammatory response syndrome (SIRS) in acute pancreatitis, resulting in multiorgan dysfunction syndrome. We tested the hypothesis that a potent PAF antagonist, lexipafant, could dampen SIRS and reduce organ failure in severe acute pancreatitis.. We conducted a randomised, double blind, placebo controlled, multicentre trial of lexipafant (100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms) involving 290 patients with an APACHE II score >6. Power calculations assumed that complications would be reduced from 40% to 24%. Secondary end points studied included severity of organ failure, markers of the inflammatory response, and mortality rate.. Overall, 80/138 (58%) patients in the placebo group and 85/148 (57%) in the lexipafant group developed one or more organ failures. The primary hypothesis was invalidated by the unexpected finding that 44% of patients had organ failure on entry into the study; only 39 (14%) developed new organ failure. Organ failure scores were reduced in the lexipafant group only on day 3: median change -1 (range -4 to +8) versus 0 (-4 to +10) in the placebo group (p=0.04). Systemic sepsis affected fewer patients in the lexipafant group (13/138 v 4/148; p=0.023). Local complications occurred in 41/138 (30%) patients in the placebo group and in 30/148 (20%) in the lexipafant group (20%; p=0.065); pseudocysts developed in 19 (14%) and eight (5%) patients, respectively (p=0.025). Deaths attributable to acute pancreatitis were not significantly different. Interleukin 8, a marker of neutrophil activation, and E-selectin, a marker of endothelial damage, decreased more rapidly in the lexipafant group (both p<0.05); however, absolute values were not different between the two groups.. The high incidence of organ failure within 72 hours of the onset of symptoms undermined the primary hypothesis, and power calculations for future studies in severe acute pancreatitis will need to allow for this. Lexipafant had no effect on new organ failure during treatment. This adequately powered study has shown that antagonism of PAF activity on its own is not sufficient to ameliorate SIRS in severe acute pancreatitis

Topics: Acute Disease; Adult; Aged; Biomarkers; Double-Blind Method; E-Selectin; Female; Humans; Imidazoles; Interleukin-8; Length of Stay; Leucine; Logistic Models; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Placebos; Platelet Activating Factor; Prospective Studies

Prophylactic administration of interleukin (IL)-10 decreases the severity of experimental pancreatitis. Prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in humans is a unique model to study the potential role of IL-10 in this setting.. In a single-center, double-blind, randomized, placebo-controlled study, the effect of a single injection of 4 microg/kg (group 1) or 20 microg/kg (group 2) IL-10 was compared with that of placebo (group 0), all administered 30 minutes before therapeutic ERCP. The primary endpoint was the effect of IL-10 on serum levels of amylases and lipases measured 4, 24, and 48 hours after ERCP. The secondary objective was to evaluate changes in plasma cytokines (IL-6, IL-8, tumor necrosis factor) at the same time points and the incidence of acute pancreatitis in the 3 groups. Subjects undergoing a first therapeutic ERCP were eligible for inclusion.. A total of 144 patients were included. Seven were excluded based on intention to treat (n = 1) or per protocol (n = 6). Forty-five, 48, and 44 patients remained in groups 0, 1, and 2, respectively. The 3 groups were comparable for age, sex, underlying disease, indication for treatment, type of treatment, and plasma levels of C-reactive protein (CRP), cytokines, and hydrolases at baseline. No significant difference was observed in CRP, cytokine, and hydrolase plasma levels after ERCP. Forty-three patients developed hyperhydrolasemia (18 in group 0, 14 in group 1, and 11 in group 2; P = 0.297), and 19 patients developed acute clinical pancreatitis (11 in group 0, 5 in group 1, 3 in group 2; P = 0.038). Two severe cases were observed in the placebo group. No mortality related to ERCP was observed. Logistic regression identified 3 independent risk factors for post-therapeutic ERCP pancreatitis: IL-10 administration (odds ratio [OR], 0.46; 95% confidence interval [95% CI], 0.22-0.96; P = 0.039), pancreatic sphincterotomy (OR, 5.04; 95% CI, 1.53-16.61; P = 0.008), and acinarization (OR, 8.19; 95% CI, 1.83-36.57; P = 0.006).. A single intravenous dose of IL-10, given 30 minutes before the start of the procedure, independently reduces the incidence of post-therapeutic ERCP pancreatitis.

Topics: Abdominal Pain; Acute Disease; Aged; Amylases; C-Reactive Protein; Cholangiopancreatography, Endoscopic Retrograde; Chronic Disease; Double-Blind Method; Female; Humans; Incidence; Injections, Intravenous; Interleukin-10; Interleukin-6; Interleukin-8; Lipase; Male; Middle Aged; Pancreatitis; Postoperative Complications; Risk Factors; Tumor Necrosis Factor-alpha

To study the concentration of interleukin 8 (IL-8) in the middle ear fluid of children with acute otitis media and the association between IL-8 concentrations, aetiology of acute otitis media, and bacteriological sterilisation.. Middle ear fluid was obtained by tympanocentesis at enrollment (day 1) and on day 4-5 in 81 children aged 3-36 months with acute otitis media who received antibiotic treatment. IL-8 concentrations were measured by enzyme linked immunosorbent assay.. 101 samples were obtained on day 1 and 47 samples on day 4-5. 94 pathogens were isolated in 79 of 101 samples obtained on day 1: 56 Haemophilus influenzae, 35 Streptococcus pneumoniae, 2 Moraxella catarrhalis, and 1 Streptococcus pyogenes. Among 40 paired, initially culture positive samples, sterilisation was achieved on day 4-5 in 22 but not in 18 (13 H influenzae, 2 S pneumoniae, and 3 H influenzae and S pneumoniae concomitantly). IL-8 was detected in 96 of 101 and 46 of 47 samples obtained on days 1 and 4-5, respectively. Mean (SD) IL-8 concentration on day 1 was significantly higher in culture positive than in negative samples (12,636 (23,317) v 5,920 (7,080) pg/ml). In paired samples, IL-8 concentration fell in 12 of 22 ears in which sterilisation was achieved and in 9 of 21 ears with persistent or new infection. Mean (SD) IL-8 concentrations on day 4-5 were significantly higher in culture positive than in negative samples (15,420 (15,418) v 6,695 (5,092) pg/ml).. Higher IL-8 concentrations are found in culture positive middle ear fluid in acute otitis media. Bacterial eradication is associated with a fall in these concentrations.

Topics: Acute Disease; Anti-Bacterial Agents; Bacterial Infections; Child, Preschool; Exudates and Transudates; Humans; Infant; Interleukin-8; Otitis Media with Effusion

Inhaled nitric oxide is used to treat hypoxia associated with acute lung injury. Endogenous nitric oxide regulates inflammatory responses, but the effect of inhaled nitric oxide therapy is unknown. We hypothesized that inhaled nitric oxide may alter inflammatory responses and endogenous nitric oxide synthase activity.. A randomized, prospective interventional study.. A university hospital's general intensive care unit.. Thirty-two patients with acute lung injury.. Patients who responded to test doses of nitric oxide were randomized to ventilator therapy with and without inhaled nitric oxide. The inhaled concentration of nitric oxide was determined by dose titration at 0, 2, 10, and 40 ppm and the minimum concentration used, which resulted in an increase in the PaO2/FIO2 ratio of at least 25%.. Patients were followed up for 30 days or until death, and bronchoalveolar lavage (BAL) was performed at 0, 24, and 72 hrs. Nitric oxide synthase activity was measured spectrophotometrically, and myeloperoxidase, elastase, interleukin-8, and leukotrienes were measured in BAL fluid by enzyme immunoassay. Total nitrite and lipid peroxides in serum were measured colorimetrically. Nitric oxide synthase activity decreased (p = .01) and total nitrite increased (p = .02) in patients receiving inhaled nitric oxide. Other markers of inflammation in BAL fluid did not change. Lipid peroxide concentrations also did not alter.. The decrease in activity of nitric oxide synthase in patients receiving nitric oxide is likely to be the result of feedback inhibition of the enzyme. This study shows that inhaled nitric oxide has no effect on several markers of the inflammatory response system and does not lead to increased oxidant stress.

Topics: Acute Disease; Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Inflammation; Interleukin-8; Leukotrienes; Lipid Peroxides; Lung; Lung Injury; Male; Middle Aged; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Pancreatic Elastase; Peroxidase; Prospective Studies; Wounds and Injuries

Cytokine-mediated interactions among the inflammatory cells may play a role in the pathogenesis of bronchial asthma. Interleukin-8 (IL-8) is a major cytokine in the recruitment of neutrophils to the area of inflammation. Serum IL-8 is a marker of disease activity and treatment efficacy in bronchial asthma. To understand the role of IL-8 in disease activity in acute asthma, changes in serum concentrations of IL-8 elaborated by activated eosinophil before and after prednisolone therapy with clinical improvement were determined in the present study. Circulating levels of IL-8 in 15 normal control subjects and in sera from 20 allergic asthmatic children with acute exacerbation and in stable condition were determined by using commercially available assay kits. The mean concentration of serum IL-8 was statistically significantly higher in asthmatic children with acute exacerbation (63.62 +/- 11.41 pg/mL) and in stable asthmatics (64.22 +/- 10.31 pg/mL) compared to the control group subjects (50.40 +/- 30.70 pg/mL; p < 0.01). However, the difference was not statistically significant between the acute exacerbation and stable asthmatics groups (p > 0.05). Serum IL-8 is a poor indicator of disease activity in acute asthma; therefore, monitoring by serum IL-8 concentration is of limited value. The clinical value of serum IL-8 as a marker of disease activity remains to be established.

Topics: Acute Disease; Adolescent; Asthma; Biomarkers; Child; Child, Preschool; Eosinophils; Humans; Interleukin-8; Leukocyte Count; Prednisolone

Familial Mediterranean fever (FMF) is a disease of unknown etiology characterized by recurrent attacks of polyserositis (peritonitis, pleuritis, and arthritis) and fever. We measured levels of soluble intercellular adhesion molecule 1 (sICAM-1) and interleukin 8 (IL-8), which are important mediators in leukocyte-endothelial adhesion and leukocyte accumulation in tissues.. sICAM-1 and IL-8 levels were studied in 30 patients with FMF during attacks and remission, along with 23 healthy and 26 disease controls. sICAM-1 and IL-8 levels were measured with commercial ELISA systems.. Median levels of sICAM-1 were significantly elevated in patients with FMF during attacks (FMF-a) and remission periods (FMF-r) compared to healthy controls (HC) (FMF-a: 600 ng/ml, FMF-r: 520 ng/ml, HC: 353 ng/ml; FMF-a vs. HC: p<0.0001, FMF-r vs. HC: p = 0.002). IL-8 levels were also significantly elevated in FMF-a compared to HC (37 vs. 25 pg/ml; p = 0.009), but not during remission (26 pg/ml; p = 0.7). A significant correlation was observed between sICAM-1 and IL-8 levels (r = 0.33, p = 0.01). sICAM-1 levels also correlated significantly with erythrocyte sedimentation rate, C-reactive protein, and fibrinogen levels of patients with FMF.. Increased levels of sICAM-1 and IL-8 in FMF suggest that neutrophils are active with increased adhesion in FMF. Since increased levels of sICAM-1 are also observed during remission, subclinical disease activity and inflammation seem to be present in some patients.

Topics: Acute Disease; Adolescent; Adult; Arthritis, Juvenile; Child; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Familial Mediterranean Fever; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Prognosis; Sensitivity and Specificity; Severity of Illness Index

We investigated whether a diet of increased carbohydrate content reduces the symptoms of acute mountain sickness (AMS) and whether concentrations of circulating cytokines rise and correlate with hypoxia and AMS. There were 19 healthy volunteers who ingested in randomized order both a high carbohydrate (68% CHO) or normal carbohydrate (45% CHO) diet for 4 d. On the 4th d, subjects were exposed to 8 h of 10% normobaric oxygen. Each subject completed the Lake Louise Consensus Questionnaire (LLCQ: a questionnaire developed to quantify the common symptoms and consequences of AMS) at the beginning and end of each hypoxic session, at which times venous blood was obtained for the following cytokines: interleukins 1 beta, 6 and 8 (IL-1 beta, IL-6, IL-8) and tumor necrosis factor alpha (TNF-alpha). AMS symptoms did not differ significantly between the diets (LLCQ scores: 68% CHO = 10.1 +/- 3.8 vs. 45% CHO = 10.3 +/- 4.1). Cytokine concentrations did not change with hypoxia on either diet, nor did individual changes correlate with AMS symptoms. We conclude that a high carbohydrate diet for 4 d does not reduce the symptoms of AMS; and plasma cytokine concentrations do not change with hypoxia and the development of AMS and, thus, are not likely mediators of this syndrome.

Topics: Acute Disease; Adolescent; Adult; Altitude Sickness; Cross-Over Studies; Dietary Carbohydrates; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Mountaineering; Oxygen; Surveys and Questionnaires; Tumor Necrosis Factor-alpha

Tumour necrosis factor (TNF) alpha, interleukin (IL) 1 beta, IL-6 and IL-8 are thought to play a central role in the pathophysiology of sepsis but their role in acute pancreatitis is unknown. In the present study, monocytes were isolated from the peripheral blood of 26 patients with moderate or severe acute pancreatitis without biliary sepsis. Secretion of these cytokines in vitro was measured at intervals during the first week of illness. Sixteen patients developed systemic complications. Peak TNF-alpha secretion was significantly higher in patients who developed systemic complications (median (interquartile range (i.q.r.)) 18.5 (5.5-28.5) ng/ml) than in those with an uncomplicated course (3.7 (2.3-6.4) ng/ml, P < 0.01). Similarly, peak IL-6 and peak IL-8 secretion were significantly higher in the complicated group (IL-6: complicated median (i.q.r.) 48.9 (12.1-71.0) ng/ml, uncomplicated 16.3 (14.2-37.9) ng/ml, P < 0.05; IL-8: complicated 748 (643-901) ng/ml, uncomplicated 608 (496-749) ng/ml), P < 0.05). No significant difference in peak IL-1 beta secretion was observed between the two groups. Systemic complications of acute pancreatitis are associated with a significant increase in monocyte secretion of TNF-alpha, IL-6 and IL-8 suggesting that, as in sepsis, these cytokines play a central role in the pathophysiology of the disease.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Monocytes; Pancreatitis; Tumor Necrosis Factor-alpha

The aims of the study were to determine whether the platelet-activating factor antagonist Lexipafant could alter the clinical course and suppress the inflammatory response of human acute pancreatitis. In a double-blind, placebo-controlled study 83 patients were randomized to receive Lexipafant 60 mg intravenously for 3 days, or placebo. Clinical progression was assessed by daily Acute Physiology And Chronic Health Evaluation (APACHE) II score and organ failure score (OFS). The magnitude of the inflammatory response on days 1-5 was assessed by serial measurement of interleukin (IL) 8, IL-6, E-selectin, polymorphonuclear elastase-alpha1-antitrypsin (PMNE-alpha 1-AT), and C-reactive protein (CRP). At entry, patients receiving Lexipafant (n = 42) or placebo (n = 41) were matched for age and sex, aetiology, APACHE II score and OFS. The disease was classified as severe in 29 patients (APACHE II score eight or more). There was a significant reduction in the incidence of organ failure (P = 0.041) and in total OFS (P = 0.048) at the end of medication (72 h). During this time seven of 12 patients with severe acute pancreatitis who had Lexipafant recovered from an organ failure; only two of 11 with severe acute pancreatitis who had placebo recovered from an organ failure and two others developed new organ failure. Lexipafant treatment significantly reduced serum IL-8 (P = 0.038), and IL-6 declined on day 1. Plasma PMNE-alpha 1-AT complexes peaked on day 1; the gradual fall to baseline over 5 days observed in controls did not occur in patients given Lexipafant. No effect was observed on serum CRP. This study provides a rationale for further clinical trials with the potent PAF antagonist Lexipafant in human acute pancreatitis.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Amylases; C-Reactive Protein; Double-Blind Method; E-Selectin; Female; Humans; Interleukin-6; Interleukin-8; Lipase; Male; Middle Aged; Pancreatitis; Platelet Activating Factor

To construct a prognostic model for severe acute pancreatitis (SAP) based on CT scores and inflammatory factors, and to evaluate its efficacy.. 128 patients with SAP diagnosed admitted to the First Hospital Affiliated to Hebei North College from March 2019 to December 2021 were enrolled and given Ulinastatin combined with continuous blood purification therapy. The levels of C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-6, IL-8), tumor necrosis factor-α (TNF-α), and D-dimer were measured before and on the third day of treatment. An abdominal CT was performed on the third day of treatment to assess the modified CT severity index (MCTSI) and extra-pancreatic inflammatory CT score (EPIC). Patients were divided into the survival group (n = 94) and the death group (n = 34) according to the 28-day survival prognosis after admission. The risk factors for the SAP prognosis were analyzed using Logistic regression, which was then used to build nomogram regression models. The value of the model was evaluated using the concordance index (C-index), calibration curves and decision curve analysis (DCA).. Before treatment, the levels of CRP, PCT, IL-6, IL-8 and D-dimer in the death group were higher than those in the survival group. After treatment, the levels of IL-6, IL-8 and TNF-α in the death group were higher than those in the survival group. MCTSI and EPIC scores in the survival group were lower than those in the death group. Logistic regression analysis shows that, pre-treatment CRP > 140.70 mg/L, D-dimer > 2.00 mg/L, and post-treatment IL-6 > 31.28 ng/L, IL-8 > 31.04 ng/L, TNF-α > 31.04 ng/L, and MCTSI > 8 points were all independent risk factors for SAP prognosis [odds ratios (OR) and 95% confidence intervals (95%CI) were 8.939 (1.792-44.575), 6.369 (1.368-29.640), 8.546 (1.664-43.896), 5.239 (1.108-24.769), 4.808 (1.126-20.525), 18.569 (3.931-87.725), all P < 0.05]. Model 1 (consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α) had a lower C-index than that model 2 (consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α, and MCTSI; 0.988 vs. 0.995). The mean absolute error (MAE) and mean square error (MSE) of model 1 (0.034, 0.003) were higher than those of model 2 (0.017, 0.001). When the threshold probability was in the range of 0-0.66 or 0.72-1.00, the net benefit of model 1 was lower than that of model 2. When the threshold probability was in the range of 0.66-0.72, the net benefit of model 1 was higher than that of model 2. In addition, model 2 had a higher C-index than acute physiology and chronic health evaluation II (APACHE II) and bedside index of acute pancreatitis severity (BISAP, 0.995 vs. 0.833, 0.751). Model 2 had a lower MAE (0.017) and MSE (0.001) than APACHE II (0.041, 0.002). Model 2 had a lower MAE than BISAP (0.025). Model 2 had a higher net benefit than both APACHE II and BISAP.. The prognostic assessment model of SAP consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α, and MCTSI has high discrimination, precision and clinical application value, and is superior to APACHE II and BISAP.

Topics: Acute Disease; C-Reactive Protein; Humans; Interleukin-6; Interleukin-8; Pancreatitis; Prognosis; Tumor Necrosis Factor-alpha

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.

Topics: Action Potentials; Acute Disease; Aged; Anti-Bacterial Agents; Biomarkers; Convalescence; COVID-19; COVID-19 Drug Treatment; Darunavir; Drug Combinations; Guillain-Barre Syndrome; Humans; Hydroxychloroquine; Immunoglobulins, Intravenous; Interleukin-6; Interleukin-8; Lopinavir; Male; Neural Conduction; Peripheral Nervous System; Prognosis; Respiratory Insufficiency; Ritonavir; SARS-CoV-2

Topics: Acute Disease; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; C-Reactive Protein; COVID-19; COVID-19 Drug Treatment; Humans; Interleukin-8; Prospective Studies; SARS-CoV-2; Serum Amyloid P-Component; Survival Rate; Ventilators, Mechanical

Acute gouty arthritis is an auto-inflammatory disease caused by the deposition of monosodium urate (MSU) crystals in joints or tissues. Excessive neutrophil recruitment into gouty lesions is a general clinical sign and induces a pain phenotype. Attenuation of successive periods of neutrophil infiltration might be a beneficial approach to achieve therapeutic efficacy. In this study, the activity of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) in attenuation of excess neutrophil infiltration was assessed in gout-induced lesions of BALB/c mice. Neutrophil infiltration in MSU-induced gouty lesions was analyzed using immunohistochemical staining. ELISA and RT-PCR were used to measure attenuation of expression of the major neutrophil chemoattractant, CXC motif chemokine ligand 8 (CXCL8), in a PLAG-treated animal model and in cells

Topics: Acute Disease; Animals; Arthritis, Gouty; Cell Movement; Diglycerides; Disease Models, Animal; Humans; Inflammation; Interleukin-8; Male; Mice; Mice, Inbred BALB C; Neutrophil Infiltration; Neutrophils; Receptors, Purinergic P2; Signal Transduction; THP-1 Cells; Uric Acid

Calcitonin gene-related peptide (CGRP) has antioxidant and anti-inflammatory activities on the pathological damage of acute pancreatitis. However, its molecular mechanism on severe acute pancreatitis (SAP) remains unknown.. To evaluate the influence of CGRP-mediated p38MAPK signaling pathway in rats with SAP.. SD rats were randomly divided into Sham group, SAP group, CGRP group (SAP rats injected with CGRP), SB203580 group (rats injected with p38MAPK pathway inhibitor SB203580), and CGRP8-37 group (SAP rats injected with CGRP8-37). Serum amylase and lipase activities were determined. Histopathological observations were evaluated, and the expression of inflammatory cytokines and oxidative stress-related indexes were measured.. Compared with Sham group, SAP rats were increased in the activities of serum amylase and lipase, the pathologic assessment of pancreatic tissue, the levels of TNF-α, IL-1β, IL-6, and IL-8, the content of MDA and MPO, and the expressions of CGRP, and p-p38MAPK protein, but they were decreased in SOD activity and GSH content. The above alterations were aggravated in the CGRP8-37 group when compared with SAP group. Besides, in comparison with SAP group, rats in the CGRP and SB203580 groups presented a reduction in the activities of serum amylase and lipase, the levels of inflammatory cytokines, the content of MDA and MPO, and the expressions of p-p38MAPK protein, while showed an elevation in SOD activity and GSH content.. Pretreatment with CGRP alleviated oxidative stress and inflammatory response of SAP rats possibly by suppressing the activity of p38MAPK pathway, and thereby postponing the disease progression.

Topics: Acute Disease; Amylases; Animals; Calcitonin Gene-Related Peptide; Cytokines; Disease Progression; Enzyme Inhibitors; Imidazoles; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Lipase; Malondialdehyde; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Pancreas; Pancreatitis; Peptide Fragments; Peroxidase; Pyridines; Random Allocation; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Signal Transduction; Tumor Necrosis Factor-alpha

Tracheitis secondary to placement of an endotracheal tube (ETT) is characterized by neutrophil accumulation in the tracheal lumen, which is generally associated with epithelial damage. Mitochondrial DNA (mtDNA), has been implicated in systemic inflammation and organ dysfunction following trauma; however, less is known about the effects of a foreign body on local trauma and tissue damage. We hypothesized that tracheal damage secondary to the ETT will result in local release of mtDNA at sufficient levels to induce TLR9 and NF-κB activation. In a swine model we compared the differences between uncoated, and chloroquine (CQ) and N-acetylcysteine (NAC) coated ETTs as measured by tracheal lavage fluids (TLF) over a period of 6 h. The swine model allowed us to recreate human conditions. ETT presence was characterized by neutrophil activation, necrosis, and release of proinflammatory cytokines mediated by TLR9/NF-κB induction. Amelioration of the tracheal damage was observed in the CQ and NAC coated ETT group as shown in tracheal tissue specimens and TLF. The role of TLR9/NF-κB dependent activity was confirmed by HEK-Blue hTLR9 reporter cell line analysis after coincubation with TLF specimens with predetermined concentrations of NAC or CQ alone or TLR9 inhibitory oligodeoxynucleotide (iODN). These findings indicate that therapeutic interventions aimed at preventing mtDNA/TLR9/NF-κB activity may have benefits in prevention of acute tracheal damage.

Topics: Acute Disease; Animals; Cell Movement; Cytokines; DNA, Mitochondrial; Epithelium; HEK293 Cells; Humans; Inflammation Mediators; Interleukin-8; Intubation, Intratracheal; Neutrophils; NF-kappa B; Pancreatic Elastase; Phenotype; Reactive Oxygen Species; Swine; Toll-Like Receptor 9; Trachea

To compare the concentration of faecal cytokines interleukin (IL)-6, -8, -10, and tumour necrosis factor (TNF)-α in dogs with acute diarrhoea with clinically normal (non-diarrhoeic) dogs.. A total of 14 dogs presenting with acute diarrhoea, and 25 dogs with no history of gastrointestinal signs in the 2 months prior to enrolment, were recruited from two veterinary hospitals in Melbourne, Australia. Concentrations of IL-6, -8, -10, and TNF-α were measured in faecal samples using canine-specific ELISA.. The diarrhoeic dogs were diagnosed with or managed for acute gastroenteritis (n = 6), extra-intestinal neoplasia (n = 2), parvoviral enteritis (n = 1), hepatopathy (n = 1), acute pancreatitis (n = 1), hypoadrenocorticism (n = 1), gastric dilatation volvulus (n = 1) and myelopathy (n = 1). IL-6 was detectable in the faeces of 10/14 (71%) diarrhoeic and 7/25 (28%) non-diarrhoeic dogs, and median concentrations were 10.8 (min 0.0, max 54.0) and 2.0 (min 0.0, max15.0) pg/mL, respectively (p = 0.01). IL-8 was detectable in the faeces of all diarrhoeic and 11 non-diarrhoeic dogs, and median concentrations were 149.7 (min 3.72, max 730.1) and 3.4 (min 0.0, max 22.5) pg/mL, respectively (p < 0.001). TNF-α was detected in the faeces of two of the diarrhoeic dogs (3.4 and 15.6 pg/mL) and none of the non-diarrhoeic dogs. IL-10 was not detected in the faeces of any dog.. Faecal concentrations of IL-6 and -8 were higher in diarrhoeic compared to non-diarrhoeic dogs, and are therefore potential candidates for non-invasive biomarkers to assess the severity and resolution of acute intestinal disease in dogs. However their correlation with disease progression and severity needs to be further investigated before their full clinical application can be determined.

Topics: Acute Disease; Animals; Biomarkers; Cytokines; Diarrhea; Dog Diseases; Dogs; Feces; Gastrointestinal Diseases; Gene Expression Regulation; Interleukin-10; Interleukin-6; Interleukin-8; Tumor Necrosis Factor-alpha

Topics: Acute Disease; Adult; Asthma; Blotting, Western; Case-Control Studies; DNA; Extracellular Traps; Female; Glucosephosphate Dehydrogenase; Humans; Inflammasomes; Interleukin-6; Interleukin-8; Longitudinal Studies; Male; Middle Aged; Neutrophils

Sulfur mustard (SM), a potent vesicating chemical warfare agent, and its analog nitrogen mustard (NM), are both strong bi-functional alkylating agents. Eyes, skin, and the respiratory system are the main targets of SM and NM exposure; however, ocular tissue is most sensitive, resulting in severe ocular injury. The mechanism of ocular injury from vesicating agents' exposure is not completely understood. To understand the injury mechanism from exposure to vesicating agents, NM has been previously employed in our toxicity studies on primary human corneal epithelial cells and ex vivo rabbit cornea organ culture model. In the current study, corneal toxicity from NM ocular exposure (1%) was analyzed for up to 28 days post-exposure in New Zealand White male rabbits to develop an acute corneal injury model. NM exposure led to conjunctival and eyelid swelling within a few hours after exposure, in addition to significant corneal opacity and ulceration. An increase in total corneal thickness and epithelial degradation was observed starting at day 3 post-NM exposure, which was maximal at day 14 post-exposure and did not resolve until 28 days post-exposure. There was an NM-induced increase in the number of blood vessels and inflammatory cells, and a decrease in keratocytes in the corneal stroma. NM exposure resulted in increased expression levels of cyclooxygenase-2, Interleukin-8, vascular endothelial growth factor and Matrix Metalloproteinase 9 indicating their involvement in NM-induced corneal injury. These clinical, biological, and molecular markers could be useful for the evaluation of acute corneal injury and to screen for therapies against NM- and SM-induced ocular injury.

Topics: Acute Disease; Animals; Chemical Warfare Agents; Cornea; Corneal Injuries; Cyclooxygenase 2; Humans; Immunohistochemistry; Interleukin-8; Male; Matrix Metalloproteinase 9; Mechlorethamine; Mustard Gas; Rabbits; Vascular Endothelial Growth Factor A

Controversy exists about the pathogenesis of idiopathic pulmonary fibrosis acute exacerbations (IPF-AEs). According to one hypothesis IPF-AEs represent the development of any etiology diffuse alveolar damage (DAD) upon usual interstitial pneumonia (UIP), whilst other researchers argue that an accelerated phase of the intrinsic fibrotic process of unknown etiology prevails, leading to ARDS. Different cytokines might be involved in both processes. The aim of this study was to assess pro-inflammatory and pro-fibrotic cytokines in the peripheral blood from stable and exacerbated IPF patients.. Consecutive IPF patients referred to our department were included. Diagnoses of IPF and IPF-AE were based on international guidelines and consensus criteria. The interleukins (IL)-4, IL-6, IL-8, IL-10, and IL-13 as well asactive transforming growth factor-beta (TGF-β) were measured in blood from both stable and exacerbated patients on the day of hospital admission for deterioration. Subjects were followed for 12months. Mann-Whitney test as well as Tobit and logistic regression analyses were applied.. Among the 41 patients studied, 23 were stable, and 18 under exacerbation; of the latter, 12 patients survived. The IL-6 and IL-8 levels were significantly higher in exacerbated patients (p=0.002 and p=0.046, respectively). An increase in either IL-6 or IL-8 by 1pg/ml increases the odds of death by 5.6% (p=0.021) and 6.7% (p=0.013), respectively, in all patients. No differences were detected for the other cytokines.. High levels of IL-6 and IL-8 characterize early-on IPF-AEs and an increase in the levels of IL-6 and IL-8 associates with worse outcome in all patients. However, as the most representative pro-fibrotic cytokines, TGF-β, IL-10, IL-4 and IL-13 were not increased and given the dualistic nature, both pro-inflammatory and pro-fibrotic of IL-6 further studies are necessary to clarify the enigma of IPF-AEs etiopathogenesis.

Topics: Acute Disease; Aged; Biomarkers; Cytokines; Female; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-6; Interleukin-8; Male; Survival Analysis

Inflammation in the setting of acute pancreatitis (AP) is partially driven by pathogen recognition receptors that recognize damage-associated molecular patterns. Interleukin (IL)-8 is a chemotactic factor produced by pathogen recognition receptor-expressing cells. A single-nucleotide polymorphism in IL8 promoter region (-251 A/T) has been implicated in inflammatory diseases. We examined whether this IL8 polymorphism confers susceptibility to AP.. Patients with AP (n = 357) were prospectively recruited. Clinical data and blood were collected in subjects and controls (n = 347). Severity was defined following the Revised Atlanta Classification. Genotypes were assessed by quantitative polymerase chain reaction using TaqMan probes.. Patients and controls had similar demographics and had no difference in Hardy-Weinberg (patients, P = 0.29; controls, P = 0.66). Twenty-five percent of patients developed severe AP. Compared with controls, the A/A genotype was more common in AP (P = 0.041; odds ratio, 1.42; 95% confidence interval, 1-1.99). Obese patients with the A/A genotype were more likely to develop mild AP (P = 0.047).. The -251 polymorphism confers susceptibility to AP and disease severity in obese patients. However, its effect is moderate. One potential mechanism for this susceptibility is via increased IL8 production by innate cells, with subsequent enhanced neutrophil influx and pancreatic injury.

Topics: Acute Disease; Adult; Aged; Alleles; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-8; Male; Middle Aged; Pancreatitis; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Prospective Studies; Risk Factors

Penicillium roqueforti is a common food and feed contaminant. However, it is also worldwide renowned for its use as a technological culture responsible for the typicity of blue-veined cheese. Members of the P. roqueforti species are also known to be able to produce secondary metabolites including mycophenolic acid (MPA) and roquefortine C (ROQ C) mycotoxins. In order to more closely simulate the reality of mycotoxin exposure through contaminated food consumption, this work investigated the toxicological effects of MPA and ROQ C not only in acute but also in chronic (i.e. 21-days continuous exposure) conditions on Caco-2 cells. Acute exposure to high MPA or ROQ C concentrations induced an increase of IL-8 secretion. Effects of 21-days continuous exposure on barrier integrity, based on concentrations found in blue-veined cheese and mean of blue cheese intake by French consumers, were monitored. Concerning exposure to ROQ C, no alteration of the intestinal barrier was observed. In contrast, the highest tested MPA concentration (780 μM) induced a decrease in the barrier function of Caco-2 cell monolayers, but no paracellular passage of bacteria was observed. This study highlighted that exposure to MPA and ROQ C average concentrations found in blue-veined cheese does not seem to induce significant toxicological effects in the tested conditions.

Topics: Acute Disease; Alkaline Phosphatase; Bacterial Translocation; Caco-2 Cells; Cheese; Chronic Disease; Enterocytes; Heterocyclic Compounds, 4 or More Rings; Humans; Indoles; Interleukin-8; Mitochondria; Mycophenolic Acid; Mycotoxins; Penicillium; Piperazines

The aim of this study was to investigate the predicting value of miR-146a/b for acute exacerbation chronic obstructive pulmonary disease (AECOPD) and COPD, and to explore their associations with inflammatory cytokines in AECOPD and stable COPD patients.One hundred six AECOPD, 122 stable COPD patients, and 110 health volunteers with age and sex matched to total COPD patients (AECOPD and stable COPD) were enrolled. Blood samples were collected from all participants. Relative expression of miR-146a/b was determined by real-time polymerase chain reaction. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), leukotriene B4 (LTB-4) expression in serum from AECOPD and stable COPD patients were assessed using commercial ELISA kit.Serum levels of miR-146a and miR-146b were down regulated in AECOPD patients compared with stable COPD patients and HCs. miR-146a and miR-146b are of good values for predicting the risk of AECOPD in HCs with AUC of 0.702 and 0.715. Additionally, miR-146a and miR-146b could distinguish AECOPD from stable COPD patients with AUC of 0.670 and 0.643. In AECOPD patients, levels of miR-146a in AECOPD patients were negatively associated with TNF-α, IL-6, IL-8, and LTE-4 expression. In stable COPD patients, miR-146a expressions were negatively correlated with TNF-α, IL-1β, IL-6, IL-8, and LTE-4 levels. And, the expressions of miR-146b in AECOPD patients were negatively associated with IL-1β and LTB-4 expression. While in stable COPD patients, miR-146b expressions were only negatively correlated with TNF-α level.In conclusion, miR-146a and miR-146b were negatively correlated with inflammatory cytokines, and could be promising biomarkers for predicting the risk of AECOPD in stable COPD patients and healthy individuals.

Topics: Acute Disease; Aged; Biomarkers; Case-Control Studies; Cytokines; Disease Progression; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Leukotriene B4; Male; MicroRNAs; Middle Aged; Pulmonary Disease, Chronic Obstructive; Real-Time Polymerase Chain Reaction; Risk Factors; Tumor Necrosis Factor-alpha

Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) in humans. Both diseases are considered to be immunologically mediated but the exact pathological mechanisms are still poorly understood. Neutrophils are considered the first line of defense against invading microbes but little is still known of their role in virus infections. We wanted to study the role of neutrophils in HFRS using blood and tissue samples obtained from Puumala hantavirus (PUUV)-infected patients. We found that neutrophil activation products myeloperoxidase and neutrophil elastase, together with interleukin-8 (the major neutrophil chemotactic factor in humans), are strongly elevated in blood of acute PUUV-HFRS and positively correlate with kidney dysfunction, the hallmark clinical finding of HFRS. These markers localized mainly in the tubulointerstitial space in the kidneys of PUUV-HFRS patients suggesting neutrophil activation to be a likely component of the general immune response toward hantaviruses. We also observed increased levels of circulating extracellular histones at the acute stage of the disease supporting previous findings of neutrophil extracellular trap formation in PUUV-HFRS. Mechanistically, we did not find evidence for direct PUUV-mediated activation of neutrophils but instead primary blood microvascular endothelial cells acquired a pro-inflammatory phenotype and promoted neutrophil degranulation in response to PUUV infection

Topics: Acute Disease; Cells, Cultured; Extracellular Traps; Hantaan virus; Hemorrhagic Fever with Renal Syndrome; Humans; Immunity, Innate; Interleukin-8; Kidney; Leukocyte Elastase; Microvessels; Neutrophil Activation; Neutrophils; Nitric Oxide Synthase Type III; Peroxidase

Cell damage in Acute Pancreatitis (AP) lead to release of cytokines and HMGB1 and Hsp70. While Hsp70 plays a role in cytoprotection, when released to extracellular milieu constitutes, as HMGB1, a danger signal and trigger pro-inflammatory responses. These molecules seem to be related to the clinical progression; but because no evidence exists about them as molecular network in AP development, we quantify HSP70, HMGB1, and cytokines in patients with AP and search for correlations with severity and prognosis.. Fifteen patients with AP were included. The average age was 52 years. Six patients had mild pancreatitis, 4 were moderately severe and 5 with a severe form. Blood samples were taken within the first 24 h, at 3d and 7d from the start. Serum HMGB1 and Hsp70 were determined using ELISA; TNF-α, IL-1β, IL-6, IL-8, IL-10 and IL-12p70 were determined by bead based immuassay.. Of all 15 patients recruited, 4 were women. Eight patients had APACHEII score higher than 8. Two patients died from AP related complications. Increase in serum HMGB1 and decrease of Hsp70 were associated with the severity and mortality. TNF-α, IL-6 and IL-8 were higher in patients that did not survive, in those with an APACHE II >8, and in those with severe AP.. High HMGB1 and low Hsp70 were associated with poor prognosis. Hsp70 might play a protective role in AP. TNF-α, IL-6, IL-8, HMGB1 and Hsp70 during hospital admissions might serve to evaluate risk of death due to AP.

Topics: Acute Disease; APACHE; Chronic Disease; Cytokines; Disease Progression; Female; HMGB1 Protein; HSP70 Heat-Shock Proteins; Humans; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Pancreatitis; Prognosis; Tumor Necrosis Factor-alpha; Young Adult

Streptococcus pneumoniae (Spn) is a common respiratory pathogen and a frequent cause of acute otitis media (AOM) in children. The first step in bacterial pathogenesis of AOM is the establishment of asymptomatic colonization in the nasopharynx. We studied Spn bacterial burden in conjunction with neutrophil recruitment and inflammatory gene transcription and cytokine secretion in samples of nasal wash collected from normal and otitis-prone children during health, viral upper respiratory infection without middle ear involvement (URI) and AOM. We found no significant associations between otitis-prone status and any of the measured parameters. However, Spn bacterial burden was significantly correlated with neutrophil recruitment, transcription of IL-8, TNF-α and SOD2, and secretion of TNF-α. We also found that transcription of IL-8 and TNF-α mRNA by neutrophils was significantly correlated with the secretion of these cytokines into the nasopharynx. We conclude that Spn bacterial burden in the NP is a major determinant of neutrophil recruitment to the NP and activity during URI and AOM, and that neutrophils are contributors to the secretion of IL-8 and TNF-α in the NP when the Spn burden is high.

Topics: Acute Disease; Asymptomatic Diseases; Bacterial Load; Cell Movement; Child, Preschool; Cytokines; Ear, Middle; Humans; Infant; Inflammation; Inflammation Mediators; Interleukin-8; Nasopharyngeal Diseases; Neutrophils; Otitis Media; Pneumococcal Infections; RNA, Messenger; Streptococcus pneumoniae; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Thrombospondin (TSP) 1 and 4 are extracellular matrix glycoproteins that me-\ diate cell proliferation, platelet aggregation and inflammatory response. Conflicting data addressed the\ possible contribution of TSP-1 and TSP-4 gene polymorphisms to acute myocardial infarction (AMI).. Our study aimed to examine the association of TSP-1 (N700S) and TSP-4 (A387P) genetic\ variants with the incidence of AMI in Egyptians. It also correlated TSP-1 variants to TSP-1 and TNF-α\ serum concentrations while TSP-4 variants to IL-8 concentration identifying TSPs' contribution to vascular inflammation.. Genotyping was done in 214 subjects; 114 AMI patients and 100 controls using PCR-RFLP\ analysis. Serum Tsp-1, TNF-α and IL-8 levels were measured by ELISA assay.. For TSP-4, (GC and CC) genotype distribution and the (C) allele frequency were significantly\ higher in AMI patients than controls (p = 0.0186), (p = 0.0117) respectively. In contrast, TSP-1 genotypes\ and allele frequencies showed no significant difference between AMI and controls (p = 0.7124 and p =\ 0.7201, respectively). Serum TSP-1, TNF-α and IL-8 concentrations were significantly elevated in AMI\ compared to controls (p = 0.0146, p < 0.0001 and p = 0.0057) respectively. Serum IL-8 levels had a significant difference among TSP-4 genotypes (p= 0.0368), being highest in the mutant C allele. Serum\ TSP-1 and TNF-α concentrations showed no significant difference among TSP-1 genotypes, but there\ was a positive correlation between both concentrations in AMI patients (p = 0.0014), (r = 0.4125).. TSP-4 A387P polymorphism, but not TSP-1 polymorphism, is an independent risk factor\ for AMI in the Egyptians.

Topics: Acute Disease; Adult; Case-Control Studies; Egypt; Female; Gene Frequency; Humans; Incidence; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Polymorphism, Genetic; Risk Factors; Thrombospondin 1; Thrombospondins; Tumor Necrosis Factor-alpha

Dysbiosis has been recently demonstrated in patients with ankylosing spondylitis (AS) but its implications in the modulation of intestinal immune responses have never been studied. The aim of this study was to investigate the role of ileal bacteria in modulating local and systemic immune responses in AS.. Ileal biopsies were obtained from 50 HLA-B27. Adherent and invasive bacteria were observed in the gut of patients with AS with the bacterial scores significantly correlated with gut inflammation. Impairment of the gut vascular barrier (GVB) was also present in AS, accompanied by significant upregulation of zonulin, and associated with high serum levels of LPS, LPS-BP, iFABP and zonulin. In in vitro studies zonulin altered endothelial tight junctions while its epithelial release was modulated by isolated AS ileal bacteria. AS circulating monocytes displayed an anergic phenotype partially restored by ex vivo stimulation with LPS+sCD14 and their stimulation with recombinant zonulin induced a clear M2 phenotype. Antibiotics restored tight junction function in HLA-B27 TG rats.. Bacterial ileitis, increased zonulin expression and damaged intestinal mucosal barrier and GVB, characterises the gut of patients with AS and are associated with increased blood levels of zonulin, and bacterial products. Bacterial products and zonulin influence monocyte behaviour.

Topics: Acute Disease; Acute-Phase Proteins; Adherens Junctions; Animals; Anti-Bacterial Agents; Antigens, CD; Bacteria; Caco-2 Cells; Cadherins; Carrier Proteins; Case-Control Studies; Cholera Toxin; Chronic Disease; Dysbiosis; Endothelium; Fatty Acid-Binding Proteins; Gene Expression; Haptoglobins; HLA-B27 Antigen; Human Umbilical Vein Endothelial Cells; Humans; Ileitis; Ileum; Interleukin-8; Intestinal Mucosa; Junctional Adhesion Molecule A; Lipopolysaccharides; Membrane Glycoproteins; Membrane Proteins; Monocytes; Permeability; Protein Precursors; Rats; Rats, Transgenic; RNA, Messenger; Spondylitis, Ankylosing; Tight Junctions; Up-Regulation

Patients with Acute Hypercapnic Respiratory Failure (AHRF) who are unresponsive to appropriate medical treatment, are often treated with Noninvasive Positive Pressure Ventilation (NPPV). Clinical predictors of the outcome of this treatment are scarce. Therefore, we evaluated the role of the biomarkers IL-8 and GDF-15 in predicting 28-day mortality in patients with AHRF who receive treatment with NPPV.. The study population were 46 patients treated with NPPV for AHRF. Clinical and background data was registered and blood samples taken for analysis of inflammatory biomarkers. IL-8 and GDF-15 were selected for analysis, and related to risk of 28-day mortality (primary endpoint) using Cox proportional hazard models adjusted for gender, age and various clinical parameters.. Of the 46 patients, there were 3 subgroup in regards to primary diagnosis: Acute Exacerbation of COPD (AECOPD, n = 34), Acute Heart Failure (AHF, n = 8) and Acute Exacerbation in Obesity Hypoventilation Syndrome (AEOHS, n = 4). There was significant difference in the basic characteristic of the subgroups, but not in the clinical parameters that were used in treatment decisions. 13 patients died within 28 days of admission (28%). The Hazard Ratio for 28-days mortality per 1-SD increment of IL-8 was 3.88 (95% CI 1.86-8.06, p < 0.001). When IL-8 values were divided into tertiles, the highest tertile had a significant association with 28 days mortality, HR 10.02 (95% CI 1.24-80.77, p for trend 0.03), compared with the lowest tertile. This correlation was maintained when the largest subgroup with AECOPD was analyzed. GDF-15 was correlated in the same way, but when put into the same model as IL-8, the significance disappeared.. IL-8 is a target to explore further as a predictor of 28 days mortality, in patients with AHRF treated with NPPV.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Female; Growth Differentiation Factor 15; Humans; Hypercapnia; Interleukin-8; Kaplan-Meier Estimate; Male; Middle Aged; Noninvasive Ventilation; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency; Sweden

The role of endothelium in the progression of atheromasic disease has already been demonstrated. Endothelin-1 (ET-1) is released from endothelial cells during acute and chronic vascular damage and it appears to be the strongest vasoconstrictor agent known.The aim of this study is to investigate the amount of endothelial damage in patients with unstable angina (UA), as defined by serum levels of ET-1, to verify a possible correlation with increased ischaemic damage by evaluation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin 8 (IL-8) levels.Serum levels of ET-1, IL-8 and NT-proBNP obtained from 10 patients affected by low-risk UA were compared to those belonging to eight healthy subjects. In order to compare the laboratory data pertaining to the two populations, a Student's t-test and a Mann-Whitney U test were performed.Levels of ET-1, IL-8 and NT-proBNP in samples of peripheral blood of patients affected by UA were significantly elevated, compared with those of the control group. The linear correlation analysis demonstrated a positive and significant correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP in subjects affected by UA.Early elevated levels of ET-1, IL-8 and NT-proBNP in patients with UA show a coexistence between ischaemic insults and endothelial damages. A positive and significant linear correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP confirms that an increased ischaemic insult is correlated to inflammation signs and endothelium damage signs.In patients with UA, ischaemia is always associated with a systemic immuno-mediated activity induced by acute endothelial damage. We suggest early administration of ET-1-selective receptor blockers and anti-inflammatory drugs.

Topics: Acute Disease; Adult; Angina, Unstable; Endothelial Cells; Endothelin-1; Endothelium; Female; Humans; Immunologic Factors; Inflammation; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

Periostin is a matricellular protein that interacts with various integrin molecules on the cell surface. Although periostin is expressed in inflamed colonic mucosa, its role in the regulation of intestinal inflammation remains unclear. We investigated the role of periostin in intestinal inflammation using Postn-deficient (Postn-/-) mice. Intestinal epithelial cells (IECs) were transfected by Postn small interfering RNAs. Periostin expression was determined in colon tissue samples from ulcerative colitis (UC) patients. Oral administration of dextran sulfate sodium (DSS) or rectal administration of trinitrobenzene sulfonic acid, induced severe colitis in wild-type mice, but not in Postn-/- mice. Administration of recombinant periostin induced colitis in Postn-/- mice. The periostin neutralizing-antibody ameliorated the severity of colitis in DSS-treated wild-type mice. Silencing of Postn inhibited inteleukin (IL)-8 mRNA expression and NF-κB DNA-binding activity in IECs. Tumor necrosis factor (TNF)-α upregulated mRNA expression of Postn in IECs, and recombinant periostin strongly enhanced IL-8 expression in combination with TNF-α, which was suppressed by an antibody against integrin αv (CD51). Periostin and CD51 were expressed at significantly higher levels in UC patients than in controls. Periostin mediates intestinal inflammation through the activation of NF-κB signaling, which suggests that periostin is a potential therapeutic target for inflammatory bowel disease.

Topics: Acute Disease; Animals; Antibodies, Neutralizing; Cell Adhesion Molecules; Cell Line; Colitis, Ulcerative; Colon; Cytokines; Disease Models, Animal; Enterocytes; Gene Silencing; Humans; Inflammation; Integrin alphaV; Interleukin-8; Intestines; Male; Mice, Inbred C57BL; NF-kappa B; Protein Binding; Recombinant Proteins; Signal Transduction

Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines.. Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels.. Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level.. We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis.

Topics: Acute Disease; Adult; Alanine Transaminase; Biomarkers; Cytokines; Enzyme-Linked Immunosorbent Assay; Fas Ligand Protein; Female; Hepatitis A; Hepatitis A virus; Hepatitis B; Hepatitis B virus; Humans; Interleukin-22; Interleukin-6; Interleukin-8; Interleukins; Liver Failure; Male; Middle Aged; T-Lymphocytes, Cytotoxic

To assess the concurrent and predictive validity of the Nasal Mucus Index (NMI), a novel measurement of acute respiratory infection (ARI) severity.. ARI, including the common cold and influenza, imposes a great burden on individuals and society. Previous research has attempted to assess the severity of ARI with self-reported and laboratory-based measurements. Self-reported measurements may introduce bias. Laboratory-based metrics are often expensive. Therefore, there is a need for non-self-reported, affordable, and validated ARI severity tests.. Participants (N = 719) with an ARI episode underwent nasal lavage on days 1 and 3. The samples were visually assessed for the amount of mucus present in the sample and were given a subsequent NMI score. Collected samples were further assessed for interleukin (IL) 8 values (in pg/mL) and polymorphonuclear neutrophils (PMN) per high-power field. The participants rated episode severity and nasal symptoms daily by using the validated Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21). A subset of nasal symptoms was used as an additional comparator. NMI scores were compared with same-day IL-8 level, PMN count, and WURSS-21 scores for concurrent validation purposes by using the Spearman ρ as the index of correlation. NMI scores were correlated with overall episode severity measurements to assess predictive validity. Overall episode severity was measured as the WURSS-21 area under the curve, nasal symptoms area under the curve, and episode duration.. The NMI score correlated significantly with the same-day IL-8 level (ρ = 0.443, p < 0.001), PMN count (ρ = 0.498, p < 0.001), WURSS-21 score (ρ = 0.098, p = 0.004), and nasal symptom score (ρ = 0.162, p < 0.001). No significant predictive correlations were found.. Associations with inflammatory biomarkers and self-reported severity measurements provided evidence of concurrent validity for the novel NMI score. The NMI can be used in future research as a simple, inexpensive, non-self-reported indicator of ARI severity.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Child; Female; Humans; Interleukin-8; Male; Middle Aged; Mucus; Nasal Lavage Fluid; Neutrophils; Predictive Value of Tests; Research Design; Respiratory Tract Infections; Severity of Illness Index; Surveys and Questionnaires; Young Adult

In-hospital outcomes are generally acceptable in patients with type B dissection; however, some patients present with undesirable complications, such as aortic expansion and rupture. Excessive inflammation is an independent predictor of adverse clinical outcomes.. We have investigated the underlying mechanisms of catastrophic complications after acute aortic dissection (AAD) in mice.. When angiotensin II was administered in lysyl oxidase inhibitor-preconditioned mice, AAD emerged within 24 hours. The dissection was initiated at the proximal site of the descending thoracic aorta and propagated distally into an abdominal site. Dissection of the aorta caused dilatation, and ≈70% of the mice died of aortic rupture. AAD triggered CXCL1 and granulocyte-colony stimulating factor expression in the tunica adventitia of the dissected aorta, leading to elevation of circulating CXCL1/granulocyte-colony stimulating factor levels. Bone marrow CXCL12 was reduced. These chemokine changes facilitated neutrophil egress from bone marrow and infiltration into the aortic adventitia. Interference of CXCL1 function using an anti-CXCR2 antibody reduced neutrophil accumulation and limited aortic rupture post AAD. The tunica adventitia of the expanded dissected aorta demonstrated high levels of interleukin-6 (IL-6) expression. Neutrophils were the major sources of IL-6, and CXCR2 neutralization significantly reduced local and systemic levels of IL-6. Furthermore, disruption of IL-6 effectively suppressed dilatation and rupture of the dissected aorta without any influence on the incidence of AAD and neutrophil mobilization.. Adventitial CXCL1/granulocyte-colony stimulating factor expression in response to AAD triggers local neutrophil recruitment and activation. This leads to adventitial inflammation via IL-6 and results in aortic expansion and rupture.

Topics: Acute Disease; Adventitia; Aged; Aminopropionitrile; Angiotensin II; Animals; Antibodies, Monoclonal; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Aortic Dissection; Aortic Rupture; Aortography; Chemokine CXCL1; Chemokine CXCL12; Chemotaxis, Leukocyte; Dilatation, Pathologic; Disease Models, Animal; Female; Granulocyte Colony-Stimulating Factor; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Neutrophil Activation; Neutrophil Infiltration; Neutrophils; Receptors, Interleukin-8B; Signal Transduction; Time Factors

We conducted a case-control study to clarify the asso-ciations between inflammatory cytokine, including interleukin (IL)-1b, IL-6, IL-8, and IL-10, polymorphisms and risk of acute pancreatitis. Genotyping analyses of IL-1β+3954 C/T (rs1143634), IL-1β-511 C/T (rs16944), IL-6 -174 G/C (rs1800795), IL-6 -634 C/G (rs1800796), IL-8 -251T/A (rs4073), IL-10 -1082A/G (rs1800896), and IL-10 -819C/T (rs1800871) were conducted using polymerase chain reaction-restriction fragment length of polymorphism. Unconditional logistic regression analysis was utilized to assess the potential association be-tween genotype frequencies and risk of acute pancreatitis. Multivari-ate regression analyses showed that subjects carrying the IL-8 -251 AA genotype had a significantly increased risk of acute pancreatitis, with an adjusted odds ratio (95% confidence interval) of 1.55 (1.02-2.36). However, we found no significant association between IL-1β +3954 C/T, IL-1β -511 C/T, IL-6 -174 G/C, IL-6 -174 G/C, IL-6 -634 C/G, IL-10 -1082A/G, or IL-10 -819C/T polymorphisms and risk of acute pancreatitis. We found that the IL-8 -251T/A polymorphism was associated with a higher susceptibility to acute pancreatitis in a Chinese population.

Topics: Acute Disease; Aged; Asian People; Case-Control Studies; China; Female; Genetic Predisposition to Disease; Genotype; Humans; Inflammation; Interleukin-8; Logistic Models; Male; Middle Aged; Multivariate Analysis; Pancreatitis; Polymorphism, Single Nucleotide; Risk Factors; Sequence Analysis, DNA; Tomography, X-Ray Computed

We recently identified galectin-3 (gal-3) as a new and strong fibroblast activator produced by colonic epithelial cells. Very little is known about the influence of gal-3 in inflammatory bowel disease. We, therefore, investigated the impact of gal-3 on dextran sodium sulfate (DSS)-induced colitis in a mouse model.. Colonic lamina propria fibroblasts of healthy controls were used for co-incubation studies of gal-3 with gal-1, TGF-β1, IFNγ, IL-4 and IL-10. Acute and chronic DSS colitis was induced by 3% DSS in drinking water in female Balb/c mice weighing 20-22 g. Recombinant gal-3 was expressed by the pET vector system and used for a 5-day treatment in different concentrations intraperitoneally. The distal third of the colon was used for histologic analysis. Colonic cytokine expression was determined by quantitative RT-PCR.. In vitro, gal-3 induced IL-8 secretion was significantly reduced by co-incubation with IL-10 (5 ng/ml) and IL-4 (10 ng/ml). Acute DSS-induced colitis was ameliorated by gal-3 treatment as indicated by increased colonic length and reduced weight loss compared to that of controls. In acute and chronic colitis, gal-3 treatment resulted in a significant suppression of colonic IL-6.. Gal-3 significantly reduces inflammation in acute and chronic DSS colitis in mice indicating a potential role in intestinal inflammation.

Topics: Acute Disease; Animals; Benzamides; Chronic Disease; Colitis; Colon; Cytokines; Dextran Sulfate; Disease Models, Animal; Epithelial Cells; Female; Fibroblasts; Galectin 3; Humans; Inflammation; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-8; Intestinal Mucosa; Mice; Mice, Inbred BALB C; Tyrosine

ω-3 PUFAs and polyphenols have multiple effects on inflammation in vivo and in vitro. The effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and resveratrol (RV) were investigated in LPS-stimulated peripheral blood leukocytes (PBLs) (i.e., acute inflammation) and IL-1β activated human chondrocytes (i.e., chronic inflammation). Inflammatory mediators including chemokines, cytokines, interleukins, and PGE2 were measured by multiplex analysis and gene expression was quantified by RT-PCR. In PBLs, RV decreased the secretion of PGE2, CCL5/RANTES, and CXCL8/IL-8 but increased IL-1β, IL-6, and IL-10. In contrast to RV, ω-3 PUFAs augmented the production of PGE2 and CXCL8/IL-8. EPA and DHA similarly affected the pattern of inflammatory mediators. Combination of RV and ω-3 PUFAs exerted synergistic effects on CCL5/RANTES and had additive effects on IL-6 or CXCL8/IL-8. Both ω-3 PUFAs and RV reduced catabolic gene expression (e.g., MMPs, ADAMTS-4, IL-1β, and IL-6) in activated chondrocytes. The data suggest that ω-3 PUFAs and RV differ in the regulation of acute inflammation of peripheral blood leukocytes but have common properties in modulating features related to chronic inflammation of chondrocytes.

Topics: Acute Disease; Chondrocytes; Chronic Disease; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Gene Expression Regulation; Humans; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Leukocytes; Lipopolysaccharides; Resveratrol; Stilbenes; Tumor Necrosis Factor-alpha

The aim of presented study was to investigate the influence of Lactobacillus plantarum LS/07 and inulin on the activity of β-glucuronidase enzyme, and counts of coliform and lactobacilli in fresh caecal digesta, cytokine levels (IL-6, IL-8), and trancription nuclear factor kappa beta (NFκB) activities in colon tissue and blood samples of rats with dextran sulphate sodium (DSS) induced acute colitis. The rats were randomly divided into four groups - CG, AC, AC+PRE and AC+PRO. Colitis was induced using of 5% DSS in drinking water for 7d. DSS application increased activity of β-glucuronidase (P < 0.001), increased counts of coliforms, and decreased lactobacilli counts (P < 0.05) in comparison to control group. Serum and tissue levels of IL-6 and IL-8 as well as tissue NFκB activities showed increased expression in acute colitis group. Inulin diet modified counts of microorganims and decreased β-glucuronidase activity, suppressed NFκB activities (P < 0.001) and down regulate synthesis of IL-6 (P < 0.01) in serum and colon tissue and tissue IL-8 (P < 0.05). Lactobacillus plantarum LS/07 decreased β-glucuronidase activity (P < 0.05), levels of IL-6 and IL-8 (P < 0.001). These results were consistent with the addition of histological findings. Our results indicate that dietary intake of Lactobacillus plantarum LS/07 and inulin suppressed expression observed markers, which play an important role in the inflammatory process, which predisposes their use in prevention or treatment of acute colitis.

Topics: Acute Disease; Animals; Colitis; Colon; Dextran Sulfate; Glucuronidase; Interleukin-6; Interleukin-8; Inulin; Lactobacillus plantarum; Male; NF-kappa B; Probiotics; Rats; Rats, Sprague-Dawley

Increased of proinflammatory cytokines levels, including interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) on severe acute pancreatitis causes vasodilatation, increased permeability of the wall, accumulation of fluid in lung tissue and pleural sinuses. Transudate from acute parapancreatyc clusters of hot liquid and abdomen falls into the chest cavity through microscopic defects in the diaphragm due to the formation of pathological pleural-peritoneal connections or the relevant pressure gradient between the abdominal and pleural cavities. Remediation and removal of acute parapancreatyc clusters combined with the use of a multicomponent drug infusion therapy Cytoflavin provide a reduction in the frequency of pulmonary complications of acute pancreatitis from 48.3 to 31.0%. Use of the drug Cytoflavin reduces the severity of endogenous intoxication and mortality from acute lung injury from 12.9 to 6.1%.

Topics: Acute Disease; Acute Lung Injury; Adult; Aged; Antioxidants; Capillary Permeability; Diaphragm; Drug Combinations; Exudates and Transudates; Female; Flavin Mononucleotide; Fluid Therapy; Humans; Inosine Diphosphate; Interleukin-8; Lipid Peroxidation; Lung; Male; Middle Aged; Niacinamide; Pancreas; Pancreatitis; Peritoneum; Pleura; Protective Agents; Succinates; Tumor Necrosis Factor-alpha; Vasodilation

The optimal time to fulfill the second (plastic) phase delayed early radical surgery in patients over the complicated forms of acute paraproctitis. On the 7th day after the opening of an abscess in a smear from the surface layer of the wound inflammatory regenerative cytogram type was observed in 66.8% of patients, early regenerative type--at 33.2%. On the 10th day was observed regenerative cytogram type. The dynamics of the concentration of cytokines in wound fluid on the 7th day showed a favorable course of wound healing process, without increasing the levels of proinflammatory cytokines, which allowed to perform the second stage of early delayed surgery in 7-10 days.

Topics: Abscess; Acute Disease; Adult; Female; Humans; Immunohistochemistry; Interleukin-10; Interleukin-1beta; Interleukin-4; Interleukin-8; Male; Middle Aged; Postoperative Period; Proctitis; Rectum; Tumor Necrosis Factor-alpha; Wound Healing

Rotavirus and norovirus are the most common known causes of viral gastroenteritis in children. This study examined the association between serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels and disease severity in the acute phase of rotavirus and norovirus gastroenteritis in children, and it also explored the role of fecal cytokine levels in children with viral and bacterial gastroenteritis.. This prospective study enrolled patients aged 4 months to 14 years admitted with acute gastroenteritis in a tertiary care center. Peripheral blood samples were collected for IL-6 and IL-8 assays within the first 3 days of diarrhea. Stool samples were obtained from the patients in the first 24 hours after admission.. Serum IL-6 and IL-8 were measured in children with viral (n = 66) and bacterial (n = 23) infections, and in healthy controls (n = 10). In the acute phase of gastroenteritis, a moderately positive correlation was found between serum IL-6 levels and disease severity (rs = 0.41, p < 0.01). Serum IL-8 levels correlated with the duration of fever (rs = 0.28, p = 0.03). Fecal IL-6 levels correlated with the maximum number of daily bowel movements (rs = 0.35, p < 0.05). Rotavirus infection induced significantly higher serum IL-8 levels than norovirus infection (p < 0.05). Receiver operating characteristic (ROC) curve analysis showed that absolute neutrophil count (ANC), maximum body temperature (BT), and Vesikari score were significant predictors in discriminating rotavirus from norovirus gastroenteritis.. IL-6 and IL-8 are involved in the pathogenesis of acute gastroenteritis in both rotavirus and norovirus. An ANC of less than 9000/mm(3), maximum BT of less than 38.2°C, and Vesikari score of less than 14 at the end of the course are potential predictors of norovirus infection in children compared with rotavirus gastroenteritis.

Topics: Acute Disease; C-Reactive Protein; Caliciviridae Infections; Child, Hospitalized; Child, Preschool; Feces; Female; Gastroenteritis; Humans; Infant; Interleukin-6; Interleukin-8; Male; Norovirus; Prospective Studies; Rotavirus Infections

To measure levels of various inflammation-related cytokines in the aqueous humor of patients with acute primary angle-closure (APAC) and senile cataract.. Aqueous humor samples were prospectively collected from 23 eyes (12 eyes with current APAC and 11 eyes with previous APAC) of 23 APAC patients and 15 eyes of 15 cataract patients. The levels of 15 inflammation-related cytokines in the aqueous humor of APAC and cataract subjects were measured by using the multiplex bead immunoassay technique. Data on patient demographics and preoperative intraocular pressure (IOP) were also collected for correlation analysis.. Compared with the group with previous APAC and the cataract group, the group with current APAC showed clear and significantly elevated concentrations of interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein (MCP)-1, MCP-3, and vascular endothelial growth factor (VEGF) (all P < 0.0167). The group with previous APAC and the cataract group had similar levels of cytokines. Intraocular pressure was positively correlated with IL-8 (P = 0.001), G-CSF (P = 0.002), MCP-3 (P < 0.001), and VEGF (P < 0.001).. An early "acute inflammatory" condition occurs in eyes with current APAC. In addition to controlling IOP, anti-inflammatory treatments are necessary for eyes suffering from APAC.

Topics: Acute Disease; Aged; Aqueous Humor; Cataract; Chemokine CCL2; Cytokines; Female; Glaucoma, Angle-Closure; Granulocyte Colony-Stimulating Factor; Humans; Immunoassay; Interleukin-6; Interleukin-8; Intraocular Pressure; Male; Middle Aged; Prospective Studies; Vascular Endothelial Growth Factor A

Topics: Acute Disease; Autoimmunity; Biomarkers; Female; Follow-Up Studies; Greece; Humans; Interleukin-8; Male; Middle Aged; Pericarditis; Pilot Projects; Prevalence; Prognosis; Prospective Studies; Recurrence; Time Factors

Progenitor cells (PCs) contribute to the endogenous repair mechanism after ischemic events. Interleukin-8 (IL-8) as part of the acute inflammatory reaction may enhance PC mobilization. Also, statins are supposed to alter number and function of circulating PCs. We aimed to investigate PC mobilization after acute ischemic stroke as well as its association with inflammatory markers and statin therapy. Sixty-five patients with ischemic stroke were enrolled in the study. The number of CD133+ PCs was analyzed by flow cytometry. Blood samples were drawn within 24 hours after symptom onset and after 5 days. The number of CD133+ PCs increased significantly within 5 days (p<0.001). We found no correlation between CD133+ PCs and the serum levels of IL-8, IL-6, or C-reactive protein (CRP). Multivariate analysis revealed that preexisting statin therapy correlated independently with the increase of CD133+ PCs (p=0.001). This study showed a mobilization of CD133+ PCs in patients with acute cerebral infarction within 5 days after symptom onset. The early systemic inflammatory response did not seem to be a decisive factor in the mobilization of PCs. Preexisting statin therapy was associated with the increase in CD133+ PCs, suggesting a potentially beneficial effect of statin therapy in patients with stroke.

Topics: AC133 Antigen; Acute Disease; Adult; Adult Stem Cells; Aged; Aged, 80 and over; Antigens, CD; Cerebral Infarction; Female; Glycoproteins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; Multivariate Analysis; Peptides; Phosphopyruvate Hydratase; Risk Factors; Young Adult

Osteochondral fractures are often seen on magnetic resonance imaging (MRI) of acutely injured knees, but their existence has gained little interest because of a lack of knowledge of their relation to treatment options and outcome. It is not clear whether acute phase synovial fluid (SF) concentrations of cartilage and bone markers and proinflammatory cytokines are different between traumatically injured knees with or without osteochondral fracture.. Acutely injured knees with an osteochondral fracture, particularly fractures with disrupted cortical bone, have higher concentrations of bone markers and cytokines than do knees without an osteochondral fracture.. Cross-sectional study; Level of evidence, 3.. Synovial fluid (hemarthrosis) was aspirated (median 1 day after injury) and 1.5-T MRI was performed (median 8 days after injury) in the acutely injured knee of 98 individuals (26% women; mean age, 23 years). As visualized on MRI, 39% knees had an osteochondral fracture with disrupted cortical bone, 30% had an osteochondral fracture with intact cortical bone, and 32% did not have an osteochondral fracture. Concentrations of sulfated glycosaminoglycan, ARGS aggrecan, cartilage oligomeric matrix protein, osteocalcin, secreted protein acidic and rich in cysteine (SPARC), osteopontin and proinflammatory cytokines (interleukin [IL]-1β, IL-6, IL-8, and tumor necrosis factor [TNF]-α) were analyzed.. After adjusting for days between injury and SF aspiration, age at injury, and sex, knees with any osteochondral fracture (with or without disrupted cortical bone) had significantly higher SF concentrations of TNF-α (median [interquartile range (IQR)] = 9 [7-12] pg/mL vs. 7 [5-14] pg/mL; P = .013), whereas knees with an osteochondral fracture with disrupted cortical bone had significantly higher SF concentrations (medians [IQRs]) of SPARC (492 [328-754] ng/mL vs. 407 [140-685] ng/mL; P = .030), IL-8 (278 [148-628] pg/mL vs. 138 [67-413] pg/mL; P = .028), and TNF-α (11 [7-15] pg/mL vs. 7 [5-14] pg/mL; P = .004) compared with knees without an osteochondral fracture.. In acutely injured knees with hemarthrosis, a concomitant osteochondral fracture with disrupted cortical bone is associated with a higher degree of joint inflammation.

Topics: Acute Disease; Adolescent; Adult; Arthritis; Biomarkers; Cartilage Oligomeric Matrix Protein; Cartilage, Articular; Cross-Sectional Studies; Female; Fractures, Bone; Fractures, Cartilage; Hemarthrosis; Humans; Interleukin-8; Knee Injuries; Magnetic Resonance Imaging; Male; Middle Aged; Osteonectin; Patellar Dislocation; Posterior Cruciate Ligament; Soft Tissue Injuries; Suction; Synovial Fluid; Tibial Meniscus Injuries; Time Factors; Tumor Necrosis Factor-alpha; Young Adult

Haematological and cytokine alterations in malaria are a broad and controversial subject in the literature. However, few studies have simultaneously evaluated various cytokines in a single patient group during the acute and convalescent phases of infection. The aim of this study was to sequentially characterise alterations in haematological patters and circulating plasma cytokine and chemokine levels in patients infected with Plasmodium vivax or Plasmodium falciparum from a Brazilian endemic area during the acute and convalescent phases of infection. During the acute phase, thrombocytopaenia, eosinopaenia, lymphopaenia and an increased number of band cells were observed in the majority of the patients. During the convalescent phase, the haematologic parameters returned to normal. During the acute phase, P. vivax and P. falciparum patients had significantly higher interleukin (IL)-6, IL-8, IL-17, interferon-γ, tumour necrosis factor (TNF)-α, macrophage inflammatory protein-1β and granulocyte-colony stimulating factor levels than controls and maintained high levels during the convalescent phase. IL-10 was detected at high concentrations during the acute phase, but returned to normal levels during the convalescent phase. Plasma IL-10 concentration was positively correlated with parasitaemia in P. vivax and P. falciparum-infected patients. The same was true for the TNF-α concentration in P. falciparum-infected patients. Finally, the haematological and cytokine profiles were similar between uncomplicated P. falciparum and P. vivax infections.

Topics: Acute Disease; Adult; Brazil; Case-Control Studies; Chemokine CCL4; Chemokines; Convalescence; Cytokines; Female; Granulocyte Colony-Stimulating Factor; Hematocrit; Humans; Inflammation; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-17; Interleukin-1beta; Interleukin-4; Interleukin-6; Interleukin-8; Malaria, Falciparum; Malaria, Vivax; Male; Parasitemia; Plasmodium falciparum; Plasmodium vivax; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

The diagnosis of appendicitis is difficult and resource consuming. New inflammatory markers have been proposed for the diagnosis of appendicitis, but their utility in combination with traditional diagnostic variables has not been tested. Our objective is to explore the potential of new inflammatory markers for improving the diagnosis of appendicitis.. The diagnostic properties of the six most promising out of 21 new inflammatory markers (interleukin [IL]-6, chemokine ligand [CXCL]-8, chemokine C-C motif ligand [CCL]-2, serum amyloid A [SAA], matrix metalloproteinase [MMP]-9, and myeloperoxidase [MPO]) were compared with traditional diagnostic variables included in the Appendicitis Inflammatory Response (AIR) score (right iliac fossa pain, vomiting, rebound tenderness, guarding, white blood cell [WBC] count, proportion neutrophils, C-reactive protein and body temperature) in 432 patients with suspected appendicitis by uni- and multivariable regression models.. Of the new inflammatory variables, SAA, MPO, and MMP9 were the strongest discriminators for all appendicitis (receiver operating characteristics [ROC] 0.71) and SAA was the strongest discriminator for advanced appendicitis (ROC 0.80) compared with defence or rebound tenderness, which were the strongest traditional discriminators for all appendicitis (ROC 0.84) and the WBC count for advanced appendicitis (ROC 0.89). CCL2 was the strongest independent discriminator beside the AIR score variables in a multivariable model. The AIR score had an ROC area of 0.91 and could correctly classify 58.3 % of the patients, with an accuracy of 92.9 %. This was not improved by inclusion of the new inflammatory markers.. The conventional diagnostic variables for appendicitis, as combined in the AIR score, is an efficient screening instrument for classifying patients as low-, indeterminate-, or high-risk for appendicitis. The addition of the new inflammatory variables did not improve diagnostic performance further.

Topics: Acute Disease; Aged; Appendicitis; Biomarkers; C-Reactive Protein; Chemokine CCL2; Female; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 9; Middle Aged; Peroxidase; ROC Curve; Serum Amyloid A Protein

The objective of the present study was to estimate the influence of isolated and combined acute suppurative Highmore maxillary sinusitis on the serum lactoferrin (LF) and interleukin-8 (IL-8) levels in the children. A total of 70 children at the age varying from 4 to 15 years were available for the examination. Twenty of them constituted the control group, 29 presented with acute suppurative Highmore maxillary sinusitis, in 21 cildren this condition was combined with frontitis, ethmoiditis, otitis, and adenoiditis. Serum lactoferrin and interleukin-8 levels were measured by solid phase enzyme-linked immunoassay. It was shown that all the aforementioned forms of rhinosinusitis were associated with a significant increase of the serum LF level, an universal factor inactivating the propagation of bacterial, viral, and fungal pathogens. The level of IL-8 known to activate chemotaxis was increased only in the children presenting with combined forms of suppurative Highmore maxillary sinusitis. It is concluded that this difference can be used for the purpose of dufferential diagnostics of different forms of suppurative maxillary sinusitis.

Topics: Acute Disease; Adolescent; Child; Child, Preschool; Humans; Interleukin-8; Lactoferrin; Maxillary Sinusitis; Suppuration

Otitis media (OM) is one of the most common childhood diseases. The relative contribution of complement activation in protection and pathogenesis during OM remains largely unknown. The purpose of this study was to investigate the beneficial and pathogenic contributions of complement activation in the middle ear of pediatric patients with recurrent acute otitis media (rAOM), and therefore to provide a rational approach to prevent sequelae of OM such as hearing loss.. Twenty children undergoing pressure equalization tube placement with or without adenoidectomy for rAOM were enrolled in the study. Bacterial cultures, enzyme-linked immunosorbent assay (ELISA) for complement components and cytokines and western blot for complement activation were performed on middle ear effusion (MEE) and serum samples. The levels of complement C3a, C5a and sC5-b9 in MEEs and serum samples were compared. The levels of these factors were also examined in regards to length of episode. Pearson's correlation coefficients were calculated on variables between C5a and IL-6 or IL-8. Complement gene expression in human middle ear epithelial (HMEE) cells induced by otopathogens was evaluated. Data were analyzed with Student's t test or the Mann-Whitney rank sum test. In all cases, a P value of <0.05 was set as the measure of significance.. Our data demonstrated that the complement classical/lectin, alternative and terminal pathways were activated in the middle ear of children with rAOM. Increased complement components of C3a, C5a and sC5-b9 in MEEs were detected in patients with the episode lasting more than six weeks. There was a strong correlation between C5a and IL-6 or IL-8 in the MEEs. Additionally, otopathogens induced enhanced gene expression of factor B and C3 in HMEE cells, which is beneficial for host defense against invading pathogens.. Our studies provided important new insights on how complement activation contributes to inflammatory process during rAOM. Knowledge of the activity of the complement pathway in patients with rAOM may stimulate the development of new strategies to prevent middle ear inflammatory tissue destruction by directing treatment to specific pathways within the complement cascade.

Topics: Acute Disease; Biomarkers; Blotting, Western; Child, Preschool; Cohort Studies; Complement Activation; Complement C3; Complement C5; Complement System Proteins; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Infant; Interleukin-6; Interleukin-8; Male; Middle Ear Ventilation; Otitis Media with Effusion; Polymerase Chain Reaction; Prospective Studies; Recurrence; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome

Urinary tract infection (UTI) is a common bacterial infection among infants and children. Predicting which children with upper UTI will develop long-term sequelae remains difficult. We aimed at evaluating the predictive value of urine concentrations of interleukin-6 (UIL-6) and interleukin-8 (UIL-8) in subsequent renal scarring. In the current observational prospective study, urine samples for UIL-6 and UIL-8 were obtained from two groups: 31 children with first episode of febrile UTI and 22 febrile children of other origin. UIL-6 and UIL-8 were increased in children with febrile UTI, compared to children with fever of other origin [median and range (picograms per milliliter): (1) UIL-6, 74.46 (0-168) vs. 10.51 (0-47.50), respectively, p = 0.0001; (2) UIL-8, 2,660.38 (0-13,801) vs. 0, respectively, p = 0.0001]. Renal scarring was found in 5/31 (16 %) children with acute pyelonephritis. Initial median UIL-8 values were significantly higher in children with later renal scarring than in those without renal scarring [median and range (picograms per milliliter): 6,163 (2,021-13,801) vs. 1,490.5 (0-5,737), respectively, p = 0.018]. In conclusion, UIL-8 might serve as a predictive biomarker for renal scarring after an acute episode of pyelonephritis. Since UIL-8 emerges as a renal-specific diagnostic and prognostic marker, it may be suitable as a selective screening tool for children with febrile UTI.

Topics: Acute Disease; Biomarkers; Case-Control Studies; Child; Child, Preschool; Cicatrix; Cross-Sectional Studies; Female; Fever; Humans; Infant; Infant, Newborn; Interleukin-6; Interleukin-8; Male; Predictive Value of Tests; Prognosis; Prospective Studies; Pyelonephritis

Polymorphonuclear neutrophils, the first leukocytes to infiltrate the inflamed tissue, can make important contributions to vascular inflammatory processes driving the development of atherosclerosis. We herein investigated the effects of atorvastatin and NCX 6560 (a nitric oxide (NO)-donating atorvastatin derivative that has completed a successful phase 1b study) on neutrophilic inflammation in carotid arteries of normocholesterolemic rabbits subjected to perivascular collar placement.. Atorvastatin or NCX 6560 were administered orally (5 mg/kg/day or equimolar dose) to New Zealand White rabbits for 6 days, followed by collar implantation 1 h after the last dose. Twenty-four hours later carotids were harvested for neutrophil quantification by immunostaining.. Treatment with NCX 6560 was associated with a lower neutrophil infiltration (-39.5 %), while atorvastatin did not affect neutrophil content. The result was independent of effects on plasma cholesterol or differences in atorvastatin bioavailability, which suggests an important role of NO-related mechanisms in mediating this effect. Consistent with these in vivo findings, in vitro studies showed that NCX 6560, as compared to atorvastatin, had greater inhibitory activity on processes involved in neutrophil recruitment, such as migration in response to IL-8 and IL-8 release by endothelial cells and by neutrophils themselves. Pretreatment with NCX 6560, but not with atorvastatin, reduced the ability of neutrophil supernatants to promote monocyte chemotaxis, a well-known pro-inflammatory activity of neutrophils.. Experimental data suggest a potential role of NO-releasing statins in the control of the vascular inflammatory process mediated by polymorphonuclear neutrophils.

Topics: Acute Disease; Animals; Atherosclerosis; Atorvastatin; Carotid Arteries; Cell Survival; Chemotaxis, Leukocyte; Cholesterol; Heptanoic Acids; Human Umbilical Vein Endothelial Cells; Humans; Interleukin-8; Male; Molecular Structure; Monocytes; Neutrophil Infiltration; Neutrophils; Nitric Oxide Donors; Pyrroles; Rabbits

Endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR) have been implicated in a number of complications associated with diabetes mellitus including micro- and macrovascular dysfunction. In this study we examine ER stress levels in blood cells isolated from human subjects with metabolic syndrome and in healthy controls. Total RNA and protein were isolated from leukocytes and the levels of specific ER stress markers were quantified by real-time-PCR and immunoblot analysis. Our results indicate that, compared to healthy controls, individuals with metabolic syndrome have elevated mRNA levels of genes indicative of ER stress; including spliced XBP-1 (sXBP-1), Grp78, and CHOP. Induced ER stress levels correlate with blood glucose but not plasma lipid concentration. Furthermore, in healthy individuals, a standard 75 g oral glucose challenge produced a significant elevation in spliced XBP-1 (1.3 fold), Grp78 (2.0 fold), and calreticulin (3.5 fold) mRNA 60 min post challenge and a significant increase in Grp78 (2.0 fold), calreticulin (2.7 fold) protein levels 2 h postchallenge, relative to fasting levels. The UPR was also activated ex vivo, in human leukocytes cultured in the presence of 15 mmol/l glucose, supporting a specific role for glucose. The oral glucose challenge was associated with a significant increase in the expression of inflammatory cytokines, including interleukin (IL)-1α/β, IL-6, and IL-8, that may result from ER stress. These findings suggest that there is an association between both acute and chronic dysglycemia and ER stress in humans.

Topics: Acute Disease; Adult; Calreticulin; Case-Control Studies; DNA-Binding Proteins; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Female; Glucose Tolerance Test; Heat-Shock Proteins; Humans; Hyperglycemia; Immunoblotting; Interleukin-1; Interleukin-6; Interleukin-8; Male; Metabolic Syndrome; Monocytes; Real-Time Polymerase Chain Reaction; Regulatory Factor X Transcription Factors; RNA, Messenger; Signal Transduction; Transcription Factor CHOP; Transcription Factors; Unfolded Protein Response; X-Box Binding Protein 1

We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP).. Interleukin (IL) 6, IL-8, IL-18, and tumor necrosis factor α were measured on admission and at days 1, 2, and 14 in 60 patients admitted with first attack of AP. The prediction of single-organ and multiorgan failure from the cytokine profiles was evaluated by receiver operating characteristic analyses.. Interleukin 6 and IL-8 levels were significantly higher in patients who developed renal, respiratory, and circulatory failure, as was the case for patients with multiorgan failure. Interleukin 18 levels were significantly elevated in renal and respiratory failure only. Tumor necrosis factor α was significantly elevated in all types of organ failures, except for intestinal failure.. Synchronous measurements of 4 cytokines demonstrated IL-6 and IL-8 to be predictive as early surrogate markers with regard to organ failures in AP. The fact that all of the cytokines were particularly elevated in patients with organ failures calls for evaluation of agents modifying the severe inflammatory response in patients with AP.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Cytokines; Denmark; Female; Humans; Inflammation Mediators; Interleukin-18; Interleukin-6; Interleukin-8; Logistic Models; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Predictive Value of Tests; Prospective Studies; ROC Curve; Systemic Inflammatory Response Syndrome; Time Factors; Tumor Necrosis Factor-alpha; Young Adult

Acute pyelonephritis (APN) is the most severe form of urinary tract infection, the etiopathogenesis of which is still not well understood. Previous studies demonstrated that chemotaxis of neutrophils into the tissue and across the infected epithelial layer is a key step in rapid bacterial clearance. Variations within genes encoding the major chemokine interleukin-8 and its receptors CXCR1 and CXCR2 are therefore attractive candidates for participation in genetic predisposition to APN. The aim of our study was to evaluate the association of single nucleotide polymorphisms (SNPs) -251 T/A, +781 C/T, +1633 C/T and +2767 A/T in the IL-8 gene, +2608 G/C in the CXCR1 gene and +1208 C/T in the CXCR2 gene with susceptibility to APN in the Slovak population. PCR-SSP and PCR-RFLP were used to genotype SNPs in 147 children with APN (62 with recurrent and 85 with episodic form) and 215 healthy individuals. Statistical analysis revealed significantly increased frequency of CXCR1 +2608 C allele (P = 0.0238, OR = 2.452, 95% CI = 1.147-5.243) and GC genotype (P = 0.0201, OR = 2.627, 95% CI = 1.188-5.810) and lower frequency of CXCR2 +1208 T allele (P = 0.0408, OR = 0.645, 95% CI = 0.429-0.972) and TT+TC genotypes (P = 0.0497, OR = 0.5273, 95% CI = 0.288-0.964) in patients with recurrent APN compared with healthy controls. Furthermore, the A allele of IL-8 -251 T/A SNP was also significantly overrepresented in patients with recurrent APN when compared with those with only single episode of APN (P = 0.0439, OR = 1.627, 95% CI = 1.019-2.599). Our results indicate that the minor CXCR1 +2608 C allele is associated with significantly increased susceptibility to APN in childhood, while the CXCR2 +1208 T allele confers protection from recurrent APN. Moreover, allele A of the IL-8 -251 T/A may also increase the risk of developing recurrent attacks after the first-time APN.

Topics: Acute Disease; Adolescent; Alleles; Case-Control Studies; Child; Child, Preschool; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Testing; Genome, Human; Genotyping Techniques; Humans; Infant; Interleukin-8; Male; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Pyelonephritis; Receptors, G-Protein-Coupled; Receptors, Interleukin-8B; Recurrence; Risk Factors; Slovakia; Young Adult

Acute graft-versus-host disease (GVHD) is the primary limitation of allogeneic hematopoietic cell transplantation, and once it develops, there are no reliable diagnostic tests to predict treatment outcomes. We hypothesized that 6 previously validated diagnostic biomarkers of GVHD (IL-2 receptor-α; tumor necrosis factor receptor-1; hepatocyte growth factor; IL-8; elafin, a skin-specific marker; and regenerating islet-derived 3-α, a gastrointestinal tract-specific marker) could discriminate between therapy responsive and nonresponsive patients and predict survival in patients receiving GVHD therapy. We measured GVHD biomarker concentrations from samples prospectively obtained at the initiation of treatment, day 14, and day 28, on a multicenter, randomized, 4-arm phase 2 clinical trial for newly diagnosed acute GVHD. We found that at each of 3 time points, GVHD onset, 2 weeks into treatment, and 4 weeks into treatment, a 6-protein biomarker panel predicted for the important clinical outcomes of day 28 posttherapy nonresponse and mortality at day 180 from onset. GVHD biomarker panels can be used for early identification of patients at high or low risk for treatment nonresponsiveness or death, and they may provide opportunities for early intervention and improved survival after hematopoietic cell transplantation. The study was registered in clinicaltrials.gov as NCT00224874.

Topics: Acute Disease; Adult; Aged; Biomarkers; Bone Marrow Transplantation; Elafin; Female; Graft vs Host Disease; Hepatocyte Growth Factor; Humans; Immunosuppressive Agents; Interleukin-8; Logistic Models; Male; Middle Aged; Pancreatitis-Associated Proteins; Predictive Value of Tests; Prognosis; Proteins; Randomized Controlled Trials as Topic; Receptors, Interleukin-2; Tumor Necrosis Factor-alpha; Young Adult

Topics: Acute Disease; APACHE; Biomarkers; C-Reactive Protein; Humans; Interleukin-6; Interleukin-8; Pancreatitis; Sensitivity and Specificity; Severity of Illness Index

Cigarette smoke (CS), the major cause of chronic obstructive pulmonary disease, contains a variety of oxidative components that were implicated in the regulation of Src homology domain 2-containing protein tyrosine phosphatase 2 (Shp2) activity. However, the contribution of Shp2 enzyme to chronic obstructive pulmonary disease pathogenesis remains unclear. We investigated the role of Shp2 enzyme in blockading CS-induced pulmonary inflammation. Shp2 levels were assessed in vivo and in vitro. Mice (C57BL/6) or pulmonary epithelial cells (NCI-H292) were exposed to CS or cigarette smoke extract (CSE) to induce acute injury and inflammation. Lungs of smoking mice showed increased levels of Shp2, compared with those of controls. Treatment of lung epithelial cells with CSE showed elevated levels of Shp2 associated with the increased release of IL-8. Selective inhibition or knockdown of Shp2 resulted in decreased IL-8 release in response to CSE treatment in pulmonary epithelial cells. In comparison with CS-exposed wild-type mice, selective inhibition or conditional knockout of Shp2 in lung epithelia reduced IL-8 release and pulmonary inflammation in CS-exposed mice. In vitro biochemical data correlate CSE-mediated IL-8 release with Shp2-regulated epidermal growth factor receptor/Grb-2-associated binders/MAPK signaling. Our data suggest an important role for Shp2 in the pathological alteration associated with CS-mediated inflammation. Shp2 may be a potential target for therapeutic intervention for inflammation in CS-induced pulmonary diseases.

Topics: Acute Disease; Animals; Cell Line; Disease Models, Animal; Inflammation; Interleukin-8; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Pneumonia; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Pulmonary Alveoli; Respiratory Mucosa; Smoking; Tobacco Products

Chronic obstructive pulmonary disease (COPD) is a prevalent smoking-related disease for which no disease‑altering therapies currently exist. Airway remodeling is one of the most important mechanisms in the pathogenesis of COPD and is triggered by chronic inflammation mediated by angiopoietin-1 (Ang-1), interleukin-8 (IL-8) and transforming growth factor-β1 (TGF-β1). The aim of this study was to investigate the effects of Ang-1, IL-8 and TGF-β1 on the pathogenesis of COPD. Forty-two COPD patients and 10 healthy adults (group A) were included in this study. We divided the 42 patients into 4 groups (groups B-E) according to the severity of the disease. We investigated the levels of Ang-1, IL-8 and TGF-β1 and the levels of pulmonary function (PF) in the stable and acute phases of COPD by enzyme-linked immunosorbent assay. We found statistically significant differences in the expression levels of Ang-1, IL-8 and TGF-β1 between the stable and acute phases in groups B-E. We found statistically significant differences in the expression levels of Ang-1 among all groups in the stable phase. In addition, there were statistically significant differences in the expression levels of TGF-β1 among all groups. There were statistically significant differences in the expression levels of IL-8 between group A and the other groups in the stable phase. Furthermore, in groups C-E we found higher correlations between Ang-1 and the forced expiratory volume in one second of forced vital capacity (FVC) [FEV1(%)] and FEV1/FVC(%) than between TGF-β1 and FEV1(%) and FEV1/FVC(%). We conclude that the blood vessel factor is more closely related to the pathogenesis of COPD.

Topics: Acute Disease; Angiopoietin-1; Forced Expiratory Volume; Humans; Interleukin-8; Male; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Transforming Growth Factor beta1; Vital Capacity

Diagnosis and management of the neuroinflammatory diseases of the central nervous system (CNS) are hindered by the lack of reliable biomarkers of active intrathecal inflammation. We hypothesized that measuring several putative inflammatory biomarkers simultaneously will augment specificity and sensitivity of the biomarker to the clinically useful range. Based on our pilot experiment in which we measured 18 inflammatory biomarkers in 10-fold concentrated cerebrospinal fluid (CSF) derived from 16 untreated patients with highly active multiple sclerosis (MS) we selected a combination of three CSF biomarkers, IL-12p40, CXCL13 and IL-8, for further validation.Concentrations of IL-12p40, CXCL13 and IL-8 were determined in a blinded fashion in CSF samples from an initial cohort (n = 72) and a confirmatory cohort (n = 167) of prospectively collected, untreated subjects presenting for a diagnostic work-up of possible neuroimmunological disorder. Diagnostic conclusion was based on a thorough clinical workup, which included laboratory assessment of the blood and CSF, neuroimaging and longitudinal follow-up. Receiver operating characteristic (ROC) curve analysis in conjunction with principal component analysis (PCA), which was used to combine information from all three biomarkers, assessed the diagnostic value of measured biomarkers.Each of the three biomarkers was significantly increased in MS and other inflammatory neurological disease (OIND) in comparison to non-inflammatory neurological disorder patients (NIND) at least in one cohort. However, considering all three biomarkers together improved accuracy of predicting the presence of intrathecal inflammation to the consistently good to excellent range (area under the ROC curve = 0.868-0.924).Future clinical studies will determine if a combinatorial biomarker consisting of CSF IL-12p40, CXCL13 and IL-8 provides utility in determining the presence of active intrathecal inflammation in diagnostically uncertain cases and in therapeutic development and management.

Topics: Acute Disease; Adult; Biomarkers; Case-Control Studies; Chemokine CXCL13; Female; Humans; Inflammation; Interleukin-12 Subunit p40; Interleukin-8; Longitudinal Studies; Male; Middle Aged; Multiple Sclerosis; Principal Component Analysis; ROC Curve; Spinal Cord

Activation of Toll-like receptors (TLR) seems to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Upon TLR activation the release of defensins, including human beta defensin 2 (HBD-2), may occur. In this study, we explored the innate responses in patients with respiratory failure, with and without COPD, requiring intubation and mechanical ventilation. Mini-bronchoalveolar lavage (mini-BAL) samples were collected from nonsmoker subjects without COPD (n = 10), smokers without COPD (n = 6), and smokers with COPD (n = 15). TLR4, TLR2, and HBD-2 expression was evaluated by immunocytochemistry; interleukin (IL)-8, IP-10, and HBD-2 concentrations were evaluated by enzyme-linked immunosorbent assay; chemotactic activity toward neutrophils and lymphocytes; and cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL] and by flow cytometry with anti-TLR4 and with HBD-2 depleted and not depleted mini-BAL). COPD mini-BAL showed increased neutrophil numbers, reduced neutrophil apoptosis, increased TLR4 and HBD-2 expression, increased neutrophil chemotactic activity, reduced IP-10 concentrations, and reduced lymphocyte chemotactic activity compared with those in nonsmoker subjects without COPD. In the smokers without COPD the mini-BAL showed reduced TLR4 and HBD-2 expression, higher IP-10 concentrations, and higher chemotactic activity than in patients with COPD. The blocking of TLR4 activation and HBD-2 depletion increased neutrophil apoptosis. No differences were observed for TLR2 expression and IL-8 concentrations. This study strengthens the contribution of TLR4 to promoting airway neutrophilia in COPD.

Topics: Acute Disease; Aged; Aged, 80 and over; Apoptosis; beta-Defensins; Bronchoalveolar Lavage Fluid; Chemotaxis; Female; Humans; Interleukin-8; Leukocytosis; Male; Neutrophils; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency; Smoking; Toll-Like Receptor 2; Toll-Like Receptor 4

Acute chorioamnionitis of infectious origin and chronic chorioamnionitis of immunological origin are two major placental lesions of spontaneous preterm birth with elevated amniotic fluid interleukin-6 and CXCL10 concentrations, respectively. The changes in the amniotic fluid proteome associated with intra-amniotic infection and acute chorioamnionitis are well defined, yet alterations unique to chronic chorioamnionitis remain to be elucidated. This study was conducted to determine those amniotic fluid proteins changing specifically in the presence of chronic chorioamnionitis. Amniotic fluid obtained from acute chorioamnionitis, chronic chorioamnionitis and gestational age-matched controls were analysed by two-dimensional (2D) difference in gel electrophoresis and MALDI-TOF analyses. The type of histological inflammation was used to define each condition in preterm labour cases (n = 125) and term not in labour cases (n = 22), and the amniotic fluid concentrations of interleukin-6, CXCL8, CXCL10 and prostaglandin F(2α) were also measured by specific immunoassays. Among preterm labour cases, 31 differentially expressed proteins were identified in chronic chorioamnionitis cases as compared to both acute chorioamnionitis and control cases. Importantly, glycodelin-A, which maintains maternal tolerance against an allogeneic fetus, was decreased in chronic chorioamnionitis, while haptoglobin was increased. We report the amniotic fluid proteome of chronic chorioamnionitis for the first time, and the findings herein strongly suggest that there is a pathophysiological association between the changes of immunomodulatory proteins in the amniotic fluid and chronic chorioamnionitis, a histological manifestation of maternal anti-fetal allograft rejection.

Topics: Acute Disease; Adolescent; Adult; Amniotic Fluid; Chemokine CXCL10; Chorioamnionitis; Chronic Disease; Cross-Sectional Studies; Dinoprost; Electrophoresis, Gel, Two-Dimensional; Extraembryonic Membranes; Female; Glycodelin; Glycoproteins; Haptoglobins; Humans; Interleukin-6; Interleukin-8; Obstetric Labor, Premature; Parity; Pregnancy; Pregnancy Proteins; Proteome; Young Adult

Systemic inflammation and elevated circulating levels of the endogenous nitric oxide inhibitor asymmetrical dimethylarginine (ADMA) have been associated with increased risk in cardiogenic shock (CS). In this prospective study, we assessed, over 4 consecutive days, the changes and possible associations between vascular function, markers of inflammation, and circulating ADMA levels in patients with CS (n = 12) and postcardiotomy heart failure (n = 12, PC-HF). Vasodilator function was measured as a reactive hyperemia index (RH-index) using a finger plethysmograph. Blood samples were analyzed for plasma ADMA, interleukine-6, interleukine-8, intracellular adhesion molecule-1, and vascular adhesion molecule-1. Baseline RH-index was significantly attenuated compared with healthy controls (2.28) for both CS and PC-HF (1.35 and 1.45, respectively, P = 0.001). Although vasodilator function improved in PC-HF patients, it remained attenuated in CS. Inflammatory markers were markedly elevated followed by a significant fall during the observation period in both groups. ADMA levels increased significantly during the observation period for PC-HF, whereas no pattern of change was observed for CS. No association was found between the longitudinal changes in RH-index, markers of inflammation, or ADMA in CS. However, an improved RH-index was associated with decreasing inflammatory markers in PC-HF. ADMA correlated to arterial lactate levels and the degree of organ dysfunction in CS. In conclusion, CS and PC-HF were characterized by a marked inflammatory activation accompanied by an attenuated vasodilator function. ADMA was related to organ dysfunction and degree of hypoperfusion during CS but showed no correlations to inflammation or hampered vasodilator function. The pathogenic significance of these responses needs clarification.

Topics: Acute Disease; Aged; Aged, 80 and over; Arginine; Biomarkers; Case-Control Studies; Endothelium, Vascular; Female; Heart Failure; Humans; Inflammation; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Prospective Studies; Shock, Cardiogenic; Vascular Cell Adhesion Molecule-1; Vasodilation

Both chemokines and adhesion molecules mediate allograft rejection by recruiting leukocytes into the allograft. We investigated the association of six single nucleotide polymorphisms (SNPs) located in interleukin (IL)-8, CXCR1, CXCR2, and selectin with kidney allograft outcomes.. The promoter regions of CXCR1 and CXCR2 were sequenced directly to find SNPs. Reporter gene assay was performed to determine the transcriptional activity of CXCR2 promoter polymorphisms. The association of SNPs in IL-8, CXCR1, CXCR2, and selectin with both acute rejection and estimated glomerular filtration rate at 1-year posttransplant was analyzed in 216 donor-recipient pairs of kidney transplantation.. The donor GA/AA genotypes of CXCR1 -2668G/A (rs2671222) were associated with increased risk for acute rejection even after adjusting for covariates such as gender, diabetes, preemptive transplantation, immunosuppressive regimen, relationship with the donor, and human leukocyte antigen mismatch (adjusted odds ratio 3.56; 95% confidence interval 1.37-9.27; P=0.009). Although the transcriptional activity of the CXCR2 variant promoter was 2.6-fold higher than that of the wild-type promoter (P=0.039), no significant association was observed between CXCR2 polymorphisms and kidney allograft outcomes. SNPs of IL-8, L-selectin, and E-selectin were not associated with kidney allograft outcomes.. The donor CXCR1 -2668 GA/AA genotypes were an independent risk factor for acute rejection in kidney transplantation.

Topics: Acute Disease; Adult; E-Selectin; Female; Graft Rejection; Histocompatibility Testing; HLA Antigens; Humans; Interleukin-8; Kidney Transplantation; L-Selectin; Male; Middle Aged; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Retrospective Studies; Treatment Outcome

T cell functional plasticity helps tailor antiviral immunity during different phases of infections. We tested whether, during different phases of HBV infection, virus-specific T cells can acquire specific proinflammatory functions that could drive granulocyte/mononuclear cell liver infiltration. Multifunctional analysis of HBV-specific T cells during acute and chronic HBV infection revealed that HBV-specific T cells had the capacity to produce the neutrophil chemokine CXCL-8 but not IL-17. CXCL-8 producing T cells were detectable in the liver of chronic HBV patients with active hepatitis; while in acute HBV patients CXCL-8 production by T cells was temporally limited to the acute phase of disease, concomitant with the peak of liver inflammation. Characterization of the conditions necessary for the development of CXCL-8 producing T cells showed a requirement for IL-7 and IL-15 during T cell expansion. These data show that functional plasticity of virus-specific T cells spontaneously occurs during HBV infection and that an environment rich IL-7 and IL-15 can license T cells with the ability to produce CXCL-8 and potentially influence liver pathology.

Topics: Acute Disease; CD8-Positive T-Lymphocytes; Cells, Cultured; Chemokines; Hepatitis B; Hepatitis B virus; Humans; Interleukin-15; Interleukin-17; Interleukin-8; Liver; Neutrophils; Peptides; Species Specificity; T-Lymphocytes; Viral Proteins

To study the prevalence of leptospira in acute hepatitis syndrome and to assess interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha levels in the pathogenesis of hepatitis due to leptospiral infection. Two hundred and forty-seven consecutive cases with symptoms of acute hepatitis and 30 healthy controls were enrolled in the study and detailed clinical history was elicited from them. Enzyme-linked immunosorbent assays (ELISAs) for HAV, HBV, HCV and HEV were performed to rule out common viral aetiology of hepatitis. IgM antibodies to leptospira were detected by ELISA. IL-8 and TNF-alpha levels were estimated in leptospira-positive cases and healthy controls by ELISA. Out of 247 cases of acute hepatitis, 46 (18.62%) were observed to be positive for IgM antibodies for leptospira. The mean age of these patients was 31.99 ± 0.28 years (25 males and 21 females; M/F ratio: 1.19:1). The mean ALT, AST and ASP were raised in the majority of patients. IL-8 was found to be elevated (130.81 pg/ml) in a large majority of cases 41/46, 89.1% (P < 0.001). Patients with more severe symptoms were associated with higher levels of IL-8. One mortality was observed due to leptospira. Unpredictably, TNF-alpha level was largely suppressed (45.63 pg/ml) in most of the leptospira-positive patients in comparison with healthy controls. Leptospira-induced hepatitis should be actively looked for in patients negative for A-E viral hepatitis. IL-8 appears to play an important role in the pathogenesis of leptospiral hepatitis. High TNF-alpha should alert clinicians for aggressive in hospital management of patients.

Topics: Acute Disease; Adult; Bilirubin; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis A; Hepatitis Antibodies; Humans; India; Interleukin-8; Leptospira; Leptospirosis; Liver Function Tests; Male; Prevalence; Prothrombin Time; Tumor Necrosis Factor-alpha

Activated protein C (APC) is increasingly understood to have diverse regulatory functions in inflammation. However, the exact mechanism of action remains unclear in severe acute pancreatitis (SAP). The aim of this study was to demonstrate the effects of APC on expressions of thrombomodulin (TM) and endothelial cell protein C receptor (EPCR), and its subsequent effect on the severity of SAP.. Sprague-Dawley rats were randomly divided into four groups. The rats were given intravenous injections of APC (50, 10 microg/kg, respectively, treated groups) or saline (SAP group) just before induction of SAP. One group of rats underwent only sham operation as control group. Experimental samples were harvested at 16 h after induction. The protein and mRNA levels of matrix metalloprotease 9 (MMP-9), TM, and EPCR in pancreatic tissue were investigated. Serum tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) levels were determined. The severity of disease was evaluated by histological score of pancreatic injury, wet/dry weight ratio of pancreatic tissue, and serum amylase.. In the APC 50 microg/kg-treated group, serum TNF-alpha, IL-8, and pancreatic MMP-9 levels were decreased and the levels of pancreatic EPCR and TM were up-regulated compared with the SAP group. A significant dose-dependent relationship was found between the decreased levels of serum IL-8 and the APC-treated dosage. Furthermore, the severity of SAP was ameliorated by APC treatment.. APC could augment the anti-coagulation and anti-inflammatory activity by up-regulating EPCR and TM expressions, thus attenuating the severity of SAP.

Topics: Acute Disease; Amylases; Animals; Blood Coagulation Factors; Disease Models, Animal; Endothelial Cells; Humans; Immunohistochemistry; Injections, Intravenous; Interleukin-8; Male; Matrix Metalloproteinase 9; Pancreas; Pancreatitis; Protein C; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; RNA, Messenger; Severity of Illness Index; Taurocholic Acid; Thrombomodulin; Tumor Necrosis Factor-alpha; Up-Regulation

An increased risk of tuberculosis has been documented in humans treated with tumor necrosis factor alpha (TNFalpha)-neutralizing agents. In murine models, impaired signaling by TNF causes exacerbation of both acute and chronic infection associated with aberrant granuloma formation and maintenance. This study was undertaken to investigate immune modulation in the setting of TNF neutralization in primary and latent tuberculosis in a non-human primate model.. Cynomolgus macaques 4 years of age or older were infected with Mycobacterium tuberculosis and subjected to clinical, microbiologic, immunologic, and radiographic examinations. Monkeys were classified as having active or latent disease 6-8 months after infection, based on clinical criteria. Monkeys used in acute infection studies were randomized to receive either adalimumab (prior to and during infection) or no treatment. Monkeys with latent infection that were randomized to receive TNF-neutralizing agent were given either an inhibitor of soluble TNF, recombinant methionyl human soluble TNF receptor I (p55-TNFRI), or adalimumab. Control monkeys with latent infection were given no treatment or saline. Data from previously studied monkeys with active or latent disease were also used for comparison.. Administration of TNF-neutralizing agents prior to M tuberculosis infection resulted in fulminant and disseminated disease by 8 weeks after infection. Neutralization of TNF in latently infected cynomolgus macaques caused reactivation in a majority of animals as determined by gross pathologic examination and bacterial burden. A spectrum of dissemination was noted, including extrapulmonary disease. Surprisingly, monkeys that developed primary and reactivation tuberculosis after TNF neutralization had similar granuloma structure and composition to that of control monkeys with active disease. TNF neutralization was associated with increased levels of interleukin-12, decreased levels of CCL4, increased chemokine receptor expression, and reduced mycobacteria-induced interferon-gamma production in blood but not in the affected mediastinal lymph nodes. Finally, the first signs of reactivation often occurred in thoracic lymph nodes.. These findings have important clinical implications for determining the mechanism of TNF neutralization-related tuberculosis.

Topics: Acute Disease; Adalimumab; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Chemokine CCL4; Chronic Disease; Disease Models, Animal; Granuloma; Immunosuppression Therapy; Interferon-gamma; Interleukin-12; Interleukin-2; Interleukin-8; Macaca fascicularis; Mycobacterium tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha

Breastfeeding during the first 12 months of life confers demonstrable immunologic benefit against infective pathogens, including those of the respiratory tract. However, the mechanism by which the ingestion of human milk modifies immunologic defense against such pathogens remains elusive. Bronchiolitis, caused predominantly by respiratory syncytial virus, is the most common clinical presentation of severe upper respiratory illness requiring hospitalization in infants and remains one of the developed world's leading causes of infant mortality and morbidity over both the short and long term. The mechanism by which an early, severe case of bronchiolitis can result in the development of recurrent childhood wheeze or asthma is unclear; however, mucosal inflammation and pulmonary neutrophilia are believed to play a significant role. The aim of this study was to examine the immune response of breastfed infants hospitalized with severe bronchiolitis, compared with formula-fed controls. Nasopharyngeal aspirates (NPA) were collected from 18 infants (aged

Topics: Acute Disease; Breast Feeding; Bronchiolitis; Cell Degranulation; Chemokine CCL2; Disease Progression; Female; Humans; Immunity, Maternally-Acquired; Infant; Infant, Newborn; Interleukin-8; Male; Neutrophils; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Risk Factors; Sputum

The present study was designed to optimize diagnostics of acute cervical lymphadenitis and adenophlegmona in patients with diabetes. A total of 146 patients with suppurative diseases of the head and the neck were available for examination of whom 63 presented with complicated clinical condition. It was shown that evaluation of the interleukin status (IL-8, IL-10), early diagnosis of systemic inflammatory reaction and compensatory anti-inflammatory response as well as the use of the ultrasound visualization technique make it possible to objectively assess the patient's condition and predict the outcome of the disease taking into consideration effects of hyperglycemia in diabetic patients.

Topics: Acute Disease; Adult; Aged; Biomarkers; Cellulitis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Follow-Up Studies; Humans; Interleukin-10; Interleukin-8; Lymphadenitis; Middle Aged; Neck; Retrospective Studies; Young Adult

In this study, we investigated the therapeutic potential of diphenhydramine (DPH), a H(1) receptor antagonist, on taurocholate-induced acute pancreatitis and the underlying mechanisms involved. Rats were randomly divided into sham-operated, model, DPH-treated, octreotide-treated and the DPH plus octreotide combination therapy groups (n = 30 per group). Animals were sacrificed 3, 6 and 24 h after modeling and drug administration (n = 10 per time point) and sera, pancreas and lungs were harvested for further studies. DPH and octreotide monotherapy relieved histopathological injuries in multiple organs when compared to the model group. Combination therapy (DPH + octreotide) demonstrated better therapeutic potential than monotherapy. Data indicated that combination therapy had a better ability to reduce average mortality rates in rats, decrease the number of inflammatory cells, attenuate necrosis, upregulate the levels of amylase, TNF-alpha and IL-8 and downregulate the levels of IL-10 in the serum. Moreover, enhanced expression of Bax in the pancreas and lung were recorded suggesting a pro-apoptotic mechanism involved in the therapeutic potential of DPH. Our study demonstrated the therapeutic potential of DPH in acute pancreatitis and suggested a novel strategy for clinical management of this disease.

Topics: Acute Disease; Amylases; Animals; Apoptosis; bcl-2-Associated X Protein; Cytokines; Diphenhydramine; Histamine H1 Antagonists; Interleukin-10; Interleukin-8; Male; Octreotide; Pancreatitis; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

No validated biomarkers exist for acute graft-versus-host disease (GVHD). We screened plasma with antibody microarrays for 120 proteins in a discovery set of 42 patients who underwent transplantation that revealed 8 potential biomarkers for diagnostic of GVHD. We then measured by enzyme-linked immunosorbent assay (ELISA) the levels of these biomarkers in samples from 424 patients who underwent transplantation randomly divided into training (n = 282) and validation (n = 142) sets. Logistic regression analysis of these 8 proteins determined a composite biomarker panel of 4 proteins (interleukin-2-receptor-alpha, tumor-necrosis-factor-receptor-1, interleukin-8, and hepatocyte growth factor) that optimally discriminated patients with and without GVHD. The area under the receiver operating characteristic curve distinguishing these 2 groups in the training set was 0.91 (95% confidence interval, 0.87-0.94) and 0.86 (95% confidence interval, 0.79-0.92) in the validation set. In patients with GVHD, Cox regression analysis revealed that the biomarker panel predicted survival independently of GVHD severity. A panel of 4 biomarkers can confirm the diagnosis of GVHD in patients at onset of clinical symptoms of GVHD and provide prognostic information independent of GVHD severity.

Topics: Acute Disease; Adolescent; Adult; Aged; Biomarkers; Child; Child, Preschool; Disease-Free Survival; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hepatocyte Growth Factor; Humans; Infant; Interleukin-2 Receptor alpha Subunit; Interleukin-8; Male; Middle Aged; Predictive Value of Tests; Receptors, Tumor Necrosis Factor, Type I; Retrospective Studies; Survival Rate; Transplantation, Homologous

The objective of the study was to observe the effects of Salvia miltiorrhiza on intercellular adhesion molecule 1 (ICAM-1) protein expression in the lungs of rats with severe acute pancreatitis (SAP) or obstructive jaundice (OJ).. A total of 288 rats were used for SAP- and OJ-associated experiments. The rats were randomly divided into sham-operated, model control, and treated group. According to the difference of time points after operation, the SAP rats of each group were subdivided into 3-, 6-, and 12-hour groups, whereas the OJ rats were divided into 7-, 14-, 21-, and 28-day groups. The contents of interleukin (IL) 6, IL-18, nitric oxide, malondialdehyde, and superoxide dismutase in serum were determined, and pathological changes and ICAM-1 protein expression in the lungs were observed.. Compared with the respective model control groups, in treated groups of SAP and OJ rats, the numbers of dead rats declined; serum superoxide dismutase content significantly increased, and serum IL-18, IL-6, and malondialdehyde contents were significantly decreased; the positive staining intensity of ICAM-1 protein in the lungs decreased significantly (P < 0.05, P < 0.01, or P < 0.001); and pathological changes in the lungs were relieved.. Salvia miltiorrhiza plays a positive role in the protection of the lungs of SAP and OJ rats.

Topics: Acute Disease; Animals; Drugs, Chinese Herbal; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Jaundice, Obstructive; Lung; Malondialdehyde; Nitric Oxide; Pancreatic Diseases; Pancreatitis; Plant Preparations; Pneumonia; Rats; Salvia miltiorrhiza; Severity of Illness Index; Superoxide Dismutase

Activated polymorphonuclear neutrophilic leukocytes (PMN) are able to produce large quantities of bactericidal molecules such as reactive oxygen species (ROS) that are associated with tissue damage in models of inflammatory mastitis. In this study, the putative protective effect of retinoid was evaluated in a lipopolysaccharide (LPS) induced mastitis model in rats. Commencing at 10 d of gestation, retinoid (dissolved in olive oil) or an equal volume of olive oil were administered daily by gavage to pregnant rats until parturition. LPS or pyrogen-free physiological saline were infused into the mammary gland 72 h after parturition. At pre-infusion (defined as 0 h) and at 2, 4, 8, 16 and 24 h post-infusion, six rats from each group were euthanized. Retinoid administration decreased PMN accumulation in mammary alveoli, significantly decreased the level of TNF-alpha in mammary tissues and IL-8 in serum at the different time points. ROS release was significantly increased after LPS infusion and was reduced by retinoid at 16 h PI. Retinoid reduced N-acetyl-beta-D-glucosaminidase (NAGase) activity in both serum and mammary tissue at 8 h PI. Intercellular adhesion molecule 1 (ICAM-1) mRNA expression reached its peak value earlier in retinoid treated rats than in the control group. Overall, the results suggest that activated PMN play an important role in the pathogenesis of acute mastitis and retinoid administration may be an effective tool for protecting mammary tissue against PMN-induced oxidative stress during LPS-induced acute mastitis.

Topics: Acetylglucosaminidase; Acute Disease; Animals; Disease Models, Animal; Female; Intercellular Adhesion Molecule-1; Interleukin-8; Lipopolysaccharides; Mammary Glands, Animal; Mastitis; Neutrophils; Oxidative Stress; Peroxidase; Pregnancy; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Retinoids; Tumor Necrosis Factor-alpha

Alloiococcus otitidis is a newly discovered organism frequently detected in otitis media. However, the association of the organism with the development of otitis media has not been disclosed in detail yet. In the middle ear, proinflammatory cytokines and chemokines are released in association with infection by pathogens, and these cytokines contribute to the induction of an inflammatory reaction. To investigate the profile of inflammation-related cytokines in the acute phase of A. otitidis infection, we analyzed the release of proinflammatory cytokines and chemokines in middle ear effusions of acute otitis media due to A. otitidis, in comparison with acute otitis media due to the well-known Gram-positive middle ear pathogen Streptococcus pneumoniae. The amounts of proinflammatory cytokines (IL-8, IL-1beta, IL-6, TNF-alpha) and CXC chemokines (IP-10, I-TAC) were significantly increased in the A. otitidis group as well as in the S. pneumoniae group. Various inflammation-related cytokines/chemokines were induced in the A. otitidis-infected middle ear, and the profile of cytokines was very similar to that in S. pneumoniae infection. This preliminary study suggests that A. otitidis has the potential to induce these cytokines, contributing to the development of an inflammatory reaction in the middle ear cavity in a similar manner to S. pneumoniae.

Topics: Acute Disease; Bacterial Infections; Chemokine CXCL11; Chemokine CXCL9; Child; Child, Preschool; Ear, Middle; Female; Gram-Negative Bacteria; Humans; Infant; Interleukin-8; Male; Otitis Media; Tumor Necrosis Factor-alpha

Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission. Nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (SIV)-rhesus macaque (Macacca mulatta) model point to opportunities at the earliest stages of infection in which a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry. Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3alpha (also known as CCL20), plasmacytoid dendritic cells and CCR5(+ )cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruits CD4(+) T cells to fuel this obligate expansion. We then show that glycerol monolaurate-a widely used antimicrobial compound with inhibitory activity against the production of MIP-3alpha and other proinflammatory cytokines-can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo it can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This new approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for the development of effective interventions to block HIV-1 mucosal transmission.

Topics: Acute Disease; Animals; Body Fluids; CD4-Positive T-Lymphocytes; Cell Cycle Proteins; Cervix Uteri; Chemokine CCL20; Dendritic Cells; Female; Gene Expression Profiling; GPI-Linked Proteins; HIV-1; Interleukin-8; Laurates; Macaca mulatta; Membrane Proteins; Monoglycerides; Mucous Membrane; Receptors, CCR5; RNA, Viral; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Time Factors; Vagina

To explore the dynamic changes of serum interleukin-6 (IL-6) and IL-8 in acute traumatic brain injury (TBI) and their correlations to the severity of brain injury and the condition of the patients.. Thirty-four patients with acute TBI were divided into two groups according to the Glasgow Coma Scale (GCS) score, clinical manifestations and the imaging data, namely patients with GCS score < or = 8 and those with GCS score between 9 and 12. Radioimmunoassay was employed to determine the serum levels of IL-6 and IL-8 at 6 different time points within 15 days after the injury in the two groups.. The serum IL-6 reached the peak level on the second day after the injury in patients with GCS score < or = 8 and on the 7th day in patients with GCS score of 9-12, showing significant differences in IL-6 variations between the two groups (P=0.046). The peak serum level of IL-8 occurred on the 7th day in patients with GCS score < or = 8 and on the 3rd day in patients with GCS score of 9-12, also showing significant differences (P=0.045). The peak level of IL-6 on the second day after the injury was significantly higher than the peak level of IL-8 that occurred on the 7th day, demonstrating significant differences in the variations of IL-6 and IL-8 after the injury (P=0.000).. The changes of serum IL-6 and IL-8 levels show positive correlations to the severity of the condition of the patients sustaining TBI. IL-6 variation is more obvious than that of IL-8 without intimate correlations between them. Clinically, serum IL-6 level can be more informative than serum IL-8 level in evaluating the changes of the condition of the TBI patients in early stage following the injury.

Topics: Acute Disease; Adolescent; Adult; Brain Injuries; Child; Female; Glasgow Coma Scale; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Trauma Severity Indices; Young Adult

Intensive insulin therapy, aiming for strict normoglycaemia, is associated with increased survival in critically ill patients. Insulin therapy concomitantly reduces plasma-free fatty acids. Recent studies indicate that free fatty acids mediate inflammation. In addition to plasma glucose and free fatty acid-lowering effects, insulin also has anti-inflammatory properties. This study was designed to study the pro-inflammatory effects of two free fatty acid concentrations during acute endotoxaemia and controlled comparable levels of plasma glucose and insulin. Twenty pigs were anaesthetized and mechanically ventilated. Pigs were randomized to two different, constant Intralipid infusion rates, throughout observation. All pigs were administered continuous intravenous infusion of endotoxin and subjected to controlled levels of p-glucose (4.5 mmol/l) and insulin by use of a hyperinsulinaemic euglycaemic clamp. Changes in circulating tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, leucocytes, insulin, glucose, free fatty acids, triglycerides, albumin, blood gases, temperature, and, haemodynamic function were monitored. Immediately following killing, biopsies were taken from heart and kidney. Biopsies were analysed for protein content of TNF-alpha, IL-6, IL-8 and IL-10. Sustained elevated and significantly different plasma levels of free fatty acids were demonstrated between groups (mean free fatty acid concentrations, 1.62 mM versus 0.58 mM, p < 0.0002). Endotoxaemia induced a steep increase in plasma TNF-alpha, IL-6 and leucocytes, however, without differences between the low- and high-free fatty acid groups. Cytokine content in heart and kidney tissue was not modified by free fatty acids. Compared with the response obtained at lower free fatty acid levels, high free fatty acid levels did not exacerbate the inflammatory response to acute endotoxaemia. Our results do not support the role of free fatty acids as a significant pro-inflammatory mediator.

Topics: Acute Disease; Animals; Blood Glucose; Cytokines; Endotoxemia; Endotoxins; Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Female; Infusions, Intravenous; Insulin; Interleukin-10; Interleukin-6; Interleukin-8; Kidney; Lipopolysaccharides; Myocardium; Swine; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

Acute irritant-induced asthma (IrIa) or reactive airways dysfunction syndrome is caused by exposure to a high concentration of an agent. The long-term pathologic consequences of IrIa remain thus far unknown.. The aim of our study was to investigate the chronic airway inflammation and remodeling that occur in association with IrIa.. Ten subjects with a history of IrIa (mean interval of 10.9 years, minimum of 4 years, since the inhalational accident) underwent bronchoscopy followed by bronchoalveolar lavage and bronchial biopsies. Immunologic and morphologic data from patients with IrIa were compared with those of patients with mild to moderate asthma as well as healthy controls.. Bronchoalveolar lavage fluid analysis showed increased eosinophil and neutrophil counts in 30% and 60% of subjects with IrIa, respectively. In the supernatant of bronchoalveolar lavage, we found a significant increase in the majority of mediators compared with healthy subjects and a significant increase in eosinophilic cationic protein, IL-8, basic fibroblast growth factor, and matrix metalloproteinase 1 compared with control patients with asthma. Evaluation of basement membrane thickness (subepithelial fibrosis) demonstrated a significant increase in patients with IrIa compared with healthy subjects and subjects with asthma. Basement membrane thickness also significantly correlated with the PC(20) value. The epithelial cell detachment showed an elevated although not significant trend compared with subjects with asthma and control subjects. Immunocytochemical analysis demonstrated increases in the number of eosinophil cationic protein and TGF-beta1-positive cells compared with healthy controls.. This study provides evidence of a significant eosinophilic and neutrophilic inflammation as well as remodeling in IrIa many years after an inhalational accident.

Topics: Acute Disease; Adult; Aged; Asthma; Bronchoalveolar Lavage Fluid; Chronic Disease; Eosinophil Cationic Protein; Eosinophils; Female; Fibroblast Growth Factors; Humans; Inflammation; Interleukin-8; Irritants; Lung; Male; Matrix Metalloproteinase 1; Middle Aged; Neutrophils; Surveys and Questionnaires; Transforming Growth Factor beta1

Cytokines play a major role in renal scar formation following febrile urinary tract infection (UTI). We investigated the role of dexamethasone combined with antibiotics in diminishing urinary interleukin-6 (UIL-6) and UIL-8 concentrations during the acute phase of pyelonephritis compared with standard antibiotic therapy. UIL-6 and UIL-8 concentrations were determined by enzyme immunoassay in 34 children with pyelonephritis who were treated with ceftriaxone plus dexamethasone (case group) and in 20 patients with the same diagnosis treated with ceftriaxone alone (control group). Urine samples were obtained at the time of presentation prior to drug administration and at follow-up 72 h after initiation of medication. Creatinine concentrations were also determined, and cytokine/creatinine ratios were calculated to standardize samples. Differences between cytokine/creatinine ratios in initial and follow-up urine samples were significant in the case group (P < 0.001) but not for controls. In addition, combined antibiotic and dexamethasone significantly decreased UIL-6 and UIL-8 concentrations compared with antibiotic alone (P < 0.05). We conclude that dexamethasone combined with antibiotics significantly decreases UIL-6 and UIL-8 levels in patients with acute pyelonephritis. This suggests that the clinical use of corticosteroids may prevent scar formation following febrile UTI.

Topics: Acute Disease; Ceftriaxone; Child; Child, Preschool; Cicatrix; Creatinine; Cytokines; Dexamethasone; Female; Humans; Infant; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Pyelonephritis; Urinary Tract Infections; Vesico-Ureteral Reflux

Several studies have indicated that cytokines may be involved in the pathophysiology of schizophrenia. Previous studies, however, have yielded contradictory results; in this study we assess the plasma levels of both T-helper-1 (Th1) and T-helper-2 (Th2) cytokines in patients with acute exacerbations of schizophrenia. Plasma concentrations of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and soluble receptor of interleukin-6 (sIL-6R) were measured with high sensitivity, enzyme-linked immunosorbent assays (ELISA) in patients with acute exacerbations of schizophrenia as compared with healthy controls. Patients with an acute exacerbation of schizophrenia had significantly increased production of TNF-alpha and significantly reduced production of IL-4 as compared with healthy subjects. No significant difference was observed in IL-6, sIL-6R, IL-8 and IL-10. Acute exacerbations of schizophrenia are associated with increased TNF-alpha concentrations (Th1) with concomitantly reduced concentrations of IL-4 (Th2) and a resulting increased TNF-alpha/IL-4 ratio.

Topics: Acute Disease; Adult; Control Groups; Cytokines; Diagnostic and Statistical Manual of Mental Disorders; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Interleukin-4; Interleukin-8; Male; Middle Aged; Psychiatric Status Rating Scales; Receptors, Interleukin-2; Schizophrenia; Schizophrenic Psychology; Tumor Necrosis Factor-alpha

To study the relationship between MCP-1-2518A/G, IL-8-251A/T polymorphism and acute pancreatitis (AP) in the Han population of Suzhou, China.. A case-control study was conducted to compare the distribution of genotype and genetic frequency of MCP-1-2518A/G, IL-8-251A/T gene polymorphism among AP (n = 101), including mild AP (n = 78) and severe AP (n = 23) and control healthy individuals (n = 120) with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing, and analyze the relationship between the MCP-1-2518A/G, IL-8-251A/T gene polymorphism and the susceptibility to AP.. Significant differences were found in the distribution of genotype of MCP-1-2518A/G between the healthy control group and mild AP group (chi2 = 32.015, P < 0.001), the same was evident between the healthy control group and severe AP group (chi2 = 12.932, P < 0.05) in Suzhou. However, no difference of genotypic distribution was noted between MAP and SAP (chi2 = 0.006, P = 0.997). The genetic frequencies of G allele in mild AP were 72.4% (113/156) and 76.1% (35/46) in severe AP, both were higher than the controls, 47.1% (113/240) (chi2 = 24.804; P < 0.001, and chi2 = 13.005; P < 0.001), but no difference was found between severe AP and mild AP (chi2 = 0.242; P = 0.623). No difference was found in the distribution of genotype of IL-8-251A/T between the healthy control group and AP group neither in the frequency of A and T allele.. The MCP-1-2518 AA genotype of the population in Suzhou may be a protective genotype of AP, while one with higher frequency of G allele is more likely to suffer from pancreatitis. But the genotype of AA and the frequency of G allele could not predict the risk of severe AP. No correlation is found between the IL-8-251 polymorphism and the liability of AP.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Asian People; Case-Control Studies; Chemokine CCL2; China; DNA Mutational Analysis; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Interleukin-8; Male; Middle Aged; Pancreatitis; Pilot Projects; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Young Adult

A 37-year-old woman presenting with high fever, dry cough and progressive dyspnea was admitted to our hospital. She took 100 mg of minocycline hydrochloride orally because of a common cold one day prior to her admission. A chest CT scan showed diffuse ground-glass opacities with interlobular septal thickening and thickening of bronchovascular bundles. An analysis of bronchoalveolar lavage fluid showed an increase in both the total cell counts and the number of eosinophils. The result of a lymphocyte stimulation test performed on peripheral blood lymphocytes was positive for minocycline. This patient had a history of pneumonia with similar clinical and radiographic findings, which had developed while receiving minocycline. As a result, we made a diagnosis of minocycline-induced acute eosinophilic pneumonia. Her symptoms and radiographic findings improved within a few days after admission. Corticosteroid therapy was effective. A marked increase of peripheral blood neutrophils were noted on admission. The serum levels of IL-8 and G-CSF increased at the early phase of the disease, but thereafter decreased in association with neutrophils, thus suggesting the contribution of these cytokines to the early phase neutrophilia in this case.

Topics: Acute Disease; Adult; Female; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-8; Leukocytosis; Minocycline; Neutrophils; Prednisolone; Pulmonary Eosinophilia; Treatment Outcome

Acute appendicitis (AA) is the most common life-threatening surgical emergency in pediatrics. To characterize the nature of the inflammatory response in AA, gene expression profiles were generated. We found remarkable uniformity in the genes that were differentially expressed between patients with appendicitis and control groups. Sixty-four probe sets were differentially expressed in samples from patients with both severe and mild appendicitis compared to control samples, and within this group we were able to identify four dominant clusters. Interestingly, expression levels of interleukin (IL)-8 significantly correlated with histologic score, and expression of IL-8 protein was observed within both neutrophils and mononuclear cells by immunohistochemistry, suggesting a possible role in the etiology of appendicitis. Although there was some overlap between genes reported to be differentially expressed in Crohn's disease (CD) and those observed in AA, differential expression of genes involved in interferon responses that characterize CD was not observed.

Topics: Acute Disease; Adolescent; Appendicitis; Child; Child, Preschool; Crohn Disease; Female; Gene Expression Profiling; Humans; Interleukin-8; Leukocytes, Mononuclear; Male; Neutrophils

Cytokines, such as interleukin (IL)-8, have been shown to be related to depressive symptoms or inflammatory diseases and may be useful as stress biomarkers.. This study was to assess whether urinary IL-8 levels were reliable indicators of stress among acute care department (AD) nurses.. A total of 118 nurses participated in the study. Urinary IL-8 levels of 49 AD nurses were compared with levels of a control group of 69 chronic care department (CD) nurses.. The urinary IL-8 levels of AD nurses, who reported a higher level of professional stress, were higher than the levels of CD nurses (P < 0.01).. Measurement of urinary IL-8 may be an appropriate biomarker for stress assessment in nurses.

Topics: Acute Disease; Adult; Attitude to Health; Biomarkers; Burnout, Professional; Chi-Square Distribution; Chronic Disease; Creatinine; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Interleukin-8; Japan; Middle Aged; Nursing Methodology Research; Nursing Staff, Hospital; Risk Factors; Statistics, Nonparametric; Surveys and Questionnaires; Work Schedule Tolerance

The aim of this study was to assess urinary interleukin-8 (IL-8) levels in pyelonephritis and its relation with the clinical course of the infection and of inflammatory changes detected by renal scintigraphy.. In this quasi-experimental before-after study, we evaluated 91 children aged 1 to 144 months (mean 34.4 +/- 35.2 months) with pyelonephritis. Inflammatory markers including erythrocyte sedimentation rate, C-reactive protein, leukocyte count, and urinary IL-8, together with the results of ultrasonography, voiding cystourethrography, and dimercaptosuccinic acid renal scintigraphy were evaluated in these children. The ratios of urinary IL-8 to creatinine (IL-8/C) before and after the treatment were compared with each other.. Urinary IL-8/C levels were significantly higher after the empirical treatment in comparison with those before the treatment (0.19 +/- 0.21 versus 0.51 +/- 0.53, P < .001). No correlation was found between the urinary IL-8 levels and leukocyturia, urine culture results, other inflammatory markers, or findings of imaging examinations.. We found high urinary IL-8 levels in children with pyelonephritis. We also documented its increasing after the treatment. We conclude that evaluation of urinary IL-8 can be a noninvasive test for diagnosis of upper urinary tract infection and its response to treatment.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Biomarkers; Child; Child, Preschool; Creatinine; Female; Humans; Infant; Interleukin-8; Male; Prospective Studies; Pyelonephritis; Pyuria

Acute bronchiolitis is the main cause of emergency visits and hospitalizations in infants. Recent data suggest that neutrophil- and eosinophil-mediated inflammations were part of bronchiolitis pathophysiology. Apart from the defined risk factors, few was known on the underlying pathophysiology, which might point out the differences observed in the severity of the disease. The aim of this study was to assess whether the clinical severity of acute epidemic bronchiolitis in young infants might be related to a specific underlying inflammatory process. Total and differential cell counts, IL-8, eotaxin, eosinophil cationic protein (ECP) and albumin levels were assessed at the time of admission in bronchial secretions from 37 infants (median age 17 wk) with acute bronchiolitis. Outcome severity variables were: hypoxemia, Silverman score, tachypnea, feeding alteration, and duration of hospitalization. Neutrophils predominated, and eosinophils were present in 54% of the infants. IL-8 levels strongly correlated with ECP and albumin levels. Albumin levels were correlated with ECP and eotaxin levels. IL-8 levels were higher in infants with hypoxemia and inversely related with SaO(2) levels. IL-8 and albumin levels significantly rose with respiratory rate, and Silverman score. IL-8, albumin and ECP levels were significantly higher in infants hospitalized >/=7 days. Furthermore, IL-8 levels were correlated with the duration of hospitalization. Neither cell counts nor eotaxin levels were related to the severity criteria studied. This study suggests that IL-8-associated airway inflammation significantly contributed to the severity of acute epidemic bronchiolitis.

Topics: Acute Disease; Albumins; Biomarkers; Bronchiolitis, Viral; Disease Outbreaks; Enzyme-Linked Immunosorbent Assay; Eosinophils; Female; France; Humans; Hypoxia; Infant; Inflammation; Interleukin-8; Length of Stay; Leukocyte Count; Male; Neutrophils; Prospective Studies; Severity of Illness Index; Sputum

The mechanisms contributing to hypoxic respiratory failure (HRF) in term infants are multifactorial. Recent evidence suggests a potential pathogenetic role for inflammation. Nitric oxide (NO), a pulmonary vasodilator, is inhibited by inflammatory mediators that are upregulated in the presence of placental inflammation.. To examine the relationship between histological chorioamnionitis and/or funisitis, serum concentrations of inflammatory mediators and severity of HRF.. Prospective observational study involving term neonates with HRF and normal controls. Blood samples were taken at birth from mixed cord blood, at 6 h and 30 h for cytokines and CRP, and at 72 h and 96 h for CRP. Placentas were examined for chorioamnionitis. The primary outcome was the administration of inhaled nitric oxide (iNO) therapy. Data were analysed using analysis of variance and chi(2) analysis.. 32 neonates with hypoxic respiratory failure and 25 controls were enrolled. 14/32 (44%) neonates with HRF required iNO, 9/32 (28%) required high-frequency ventilation and 3/32 (9%) required ECMO; 2/32 (6%) died. Neonates with HRF had more than threefold higher cord levels of interleukin 8 (IL8) than the controls (p<0.05). At 6 h and 30 h, serum IL6, IL8 and CRP were > or =2.2-fold higher in neonates who received iNO (p<0.003). 23/32 (72%) infants with HRF had evidence of histological chorioamnionitis and/or funisitis compared with 5/25 (20%) controls (p<0.001).. Severe HRF, as defined by the need for iNO, is associated with raised blood levels of proinflammatory mediators and increased occurrence of histological chorioamnionitis and funisitis, suggesting that inflammation contributes to the severity of hypoxic failure.

Topics: Acute Disease; Biomarkers; Bronchodilator Agents; C-Reactive Protein; Carbon Dioxide; Chorioamnionitis; Female; Humans; Hypoxia; Infant, Newborn; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Nitric Oxide; Oxygen; Partial Pressure; Pregnancy; Prospective Studies; Respiratory Insufficiency

Irreversibly inflamed pulp (IIP) constitutes both a pathophysiologic and a diagnostic challenge. Gingival crevicular fluid (GCF) samples were obtained with Periopaper strips from IIP and adjacent and contralateral teeth for interleukin-8 (CXCL8) and tumor necrosis factor-alpha (TNF-alpha) measurements. Pain intensity was reported by using a verbal numeric scale (1-10). TNF-alpha (n = 25) was not detectable in GCF, whereas CXCL8 (n = 17) was significantly greater in IIP (302.1 +/- 164.9 pg/mL) compared with adjacent (139 +/- 138.58 pg/mL; P = .0072) or contralateral (173.8 +/- 166.4 pg/mL; P = .0231) teeth. A subgroup of high pain (>5) patients (n = 7) had CXCL8 IIP levels (323.6 +/- 148.4 pg/mL) that were significantly different from the contralateral teeth (P = .0262); however, they did not differ from the adjacent teeth (P = .1649), suggesting that neighboring teeth might also have inflammation. Another group of patients (n = 7) who had received local anesthesia before sampling had very low IIP CXCL8 levels. GCF CXCL8 levels might be a useful measurement for staging patients with acute pulpitis.

Topics: Acute Disease; Adult; Anesthetics, Local; Female; Gingival Crevicular Fluid; Humans; Interleukin-8; Lidocaine; Male; Mandibular Nerve; Middle Aged; Nerve Block; Pain Measurement; Pulpitis; Tumor Necrosis Factor-alpha

To investigate whether the cytokine-inducing properties of surface-bound collagen type II (CII)-containing immune complexes (IC), which were reported earlier, have any clinical impact.. Anti-CII serology was analysed in 274 patients with early rheumatoid arthritis (RA). Patients with increased levels of anti-CII were followed serially for 1-5 years with regard to anti-CII IC-induced levels of tumour necrosis factor (TNF)alpha, interleukin (IL)1beta and IL8. Levels of antibodies and IC-induced cytokines were compared with clinical indices over 5 years of follow-up.. 5/100 healthy controls and 24/274 (8.8%) patients with RA exhibited increased levels (>29 arbitrary units (AU)/ml) of anti-native CII antibodies, a non-significant difference. 9/274 (3.3%) patients with RA and no controls comprised a discrete group with high anti-CII levels>450 AU/ml. These high anti-CII level sera were associated with induction of pro-inflammatory cytokines by anti-CII-containing IC formed in vitro. 8/9 patients with high baseline anti-CII levels exhibited a parallel decline in antibody levels, IC-induced cytokines, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Anti-CII-positive patients had significantly increased levels of CRP and ESR at baseline, but not later during the follow-up.. Anti-native CII-positive patients with RA have a distinct clinical phenotype characterised by an early acute phase response that might be driven by anti-CII-containing IC in joint cartilage.

Topics: Acute Disease; Antigen-Antibody Complex; Antirheumatic Agents; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Blood Sedimentation; C-Reactive Protein; Cells, Cultured; Collagen Type II; Cytokines; Female; Humans; Inflammation Mediators; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Phenotype; Prospective Studies; Severity of Illness Index; Tumor Necrosis Factor-alpha

It has been difficult to evaluate the protective efficacy of vaccine candidates against shigellosis, a major form of bacillary dysentery caused by Shigella spp. infection, because of the lack of suitable animal models. To develop a proper animal model representing human bacillary dysentery, guinea pigs were challenged with virulent Shigella flexneri serotype 2a (strains 2457T or YSH6000) or S. flexneri 5a (strain M90T) by the intrarectal (i.r.) route. Interestingly, all guinea pigs administered these Shigella strains developed severe and acute rectocolitis. They lost approximately 20% of their body weight and developed tenesmus by 24 h after Shigella infection. Shigella invasion and colonization of the distal colon were seen at 24 h but disappeared by 48 h following i.r. infection. Histopathological approaches demonstrated significant damage and destruction of mucosal and submucosal layers, thickened intestinal wall, edema, erosion, infiltration of neutrophils, and depletion of goblet cells in the distal colon. Furthermore, robust expression of IL-8, IL-1beta, and inducible NO synthase mRNA was detected in the colon from 6 to 24 h following Shigella infection. Most importantly, in our new shigellosis model, guinea pigs vaccinated with an attenuated S. flexneri 2a SC602 strain possessing high levels of mucosal IgA Abs showed milder symptoms of bacillary dysentery than did animals receiving PBS alone after Shigella infection. In the guinea pig, administration of Shigella by i.r. route induces acute inflammation, making this animal model useful for assessing the protective efficacy of Shigella vaccine candidates.

Topics: Acute Disease; Animals; Colon; Dysentery, Bacillary; Female; Gene Expression Regulation; Guinea Pigs; Immunoglobulin A; Inflammation; Interleukin-1beta; Interleukin-8; Models, Animal; Nitric Oxide Synthase; Proctocolitis; Shigella flexneri; Shigella Vaccines; Vaccines, Attenuated

We performed a case-control study in children diagnosed by the first episode of upper urinary tract infection with or without vesicoureteral reflux to evaluate the association of functional polymorphism of interleukin-8 (-251A>T and +2767A>G), and its receptor CXCR1 (+2607G>C).. Genomic DNA was obtained from 265 children with a clinical and laboratory diagnosis of urinary tract infection who were recruited in northeast Italy. The children were subdivided as 173 who were dimercapto-succinic acid scan positive with positive static renal scintigraphy in acute conditions, consistent with the diagnosis of acute pyelonephritis, and 92 who were dimercapto-succinic acid scan negative. Genetic analysis for the same polymorphisms was also extended to a control population of 106 umbilical cord DNA samples.. Statistical analysis of genotype data showed that 1) the tested populations were in Hardy-Weinberg equilibrium, 2) there were significant differences between the dimercapto-succinic acid scan positive and negative groups (p=0.049), and the dimercapto-succinic acid scan positive group vs controls (p=0.032) in terms of interleukin-8 -251A>T polymorphism frequency, 3) there was also a significant difference in the distribution of IL-8 -251A>T and +2767A>G polymorphisms between dimercapto-succinic acid scan positive and negative children in the subgroup without vesicoureteral reflux (p=0.03 and 0.02, respectively) and 4) no significant differences were found in the frequency of the distribution of CXCR1 +2607G>C polymorphism in all groups.. These data suggest that the gene for the proinflammatory chemokine interleukin-8 is involved in susceptibility to acute pyelonephritis during upper urinary tract infection in children with or without vesicoureteral reflux.

Topics: Acute Disease; Case-Control Studies; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Infant; Infant, Newborn; Interleukin-8; Male; Polymorphism, Genetic; Pyelonephritis; Receptors, Interleukin-8A; Urinary Tract Infections; Vesico-Ureteral Reflux

To investigate the effects of lycopene on T lymphocyte subpopulations and pulmonary alveolar macrophagic (PAM) functions in rats with acute lung injury (ALI).. Rats were randomly divided into the following groups. (1) Control group, (2) ALI model group, (3) Low dose group,(4) Mid dose group and (5) High dose group. Control group and ALI model group were treated with solvent of lycopene, and the other groups were gastrically incubated with lycopene. Thirty-five days later, control group were given physiological saline, ALI model group and lycopene administrated groups were injected with lipopolysaccharide (LPS) (6.0 mg/kg) to induce ALI. One hour, four hours or six hours after LPS or physiological saline challenged, abdominal aorta blood for measuring lymphocyte subpopulations and bronchoalveolar lavage fluid for measuring function of PAM were gathered respectively.. (1) At h 1, the percentages of CD3(+), CD4(+) and CD8(+) of lycopene administrated groups compared with control group were not significantly different. At h 4, the percentage of CD4(+) was similar to that at h 1. As for the percentages of CD3(+), except high dose group [(28.8+/-9.9)%] was significantly lower, low dose, mid dose and ALI model group showed no significant difference compared with control group[(39.5+/- 4.5)%]. The percentages of CD8(+) of ALI model and lycopene administrated rats, separately (10.2+/-3.9)%, (10.3+/-2.8)%, (9.8+/-2.8)%, (10.1+/-3.5)% , had been significantly reduced compared with control group[(15.1+/-2.5)%]; between ALI model and lycopene administrated groups there was no significant difference. The instance at h 6 was the same as that at h 4. The percentage ratios of CD4(+) T-lymphocyte to CD8(+) T-lymphocyte of ALI model rats were not significantly different compared with control group or lycopene administrated groups at h 1 and h 6. At h 4, the ratio of the CD4(+) and CD8(+) in Low dose and Mid dose groups had significant difference and ALI model, high dose hadn't when they were compared with control group. (2) Lycopene increased the phagocytic function of PAMs significantly at h 1(P<0.01), the optical density of PAM of control group, ALI model group, low dose group, mid dose group, high dose group was 0.136+/-0.025, 0.215+/-0.095, 0.239+/-0.052, 0.275+/-0.068 and 0.297+/-0.049; what happened at h 4 was similar to that at h 1; Phagocytic function of PAM of lycopene administrated groups was increased compared with control group. (3) The concentrations of tumor necrosis factor-alpha (TNF-alpha) in control group, ALI model group, low dose group, mid dose group, high dose groups were 1.50+/-0.30, 1.87+/-0.30, 1.76+/-0.40, 1.74+/- 0.38,1.62+/-0.35 microg/L;and those of IL-8 were 0.82+/-0.08, 0.99+/-0.14, 0.82+/-0.16, 0.84+/-0.16, 0.83+/-0.11 microg/L. The concentrations of TNF-alpha and interleukin-8 (IL-8) in BALF were decreased by lycopene, especially the levels of IL-8 were reduced significantly.. Lycopene might attenuate lipopolysaccharide-induced impairment of lungs and improve ALI prognosis by increasing the phagocytic function of PAMs significantly and restraining the secretion of TNF-alpha and IL-8.

Topics: Acute Disease; Adjuvants, Immunologic; Animals; Bronchoalveolar Lavage Fluid; Carotenoids; CD3 Complex; CD4-CD8 Ratio; Dose-Response Relationship, Drug; Interleukin-8; Lipopolysaccharides; Lung Diseases; Lycopene; Macrophages; Male; Phagocytosis; Random Allocation; Rats; Rats, Sprague-Dawley; T-Lymphocyte Subsets; Tumor Necrosis Factor-alpha

Stroke is associated with elevation of several proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-8 that are correlated with central nervous system (CNS) injury. Anti-platelet therapies are important agents in stroke management. The role of antiplatelets as anti-inflammatory agents is not known in acute stroke patients. Furthermore, their effect on induction of potential cytokines as TNF-alpha and IL-8 in those patients is still not clear. Thus, we herein examined the induction of TNF-alpha and IL-8 in acute stroke patients and examined the effects of the antiplatelets drugs aspirin, clopidogrel and dipyridamole, and piracetam in their induction. Cytokines were detected intracellularly in leukocytes from patients who had first acute ischemic stroke and from matched controls by immunocytochemistry. The results showed significant increase of spontaneously produced TNF-alpha and IL-8 in patients compared to control. This induction was significantly inhibited differently by each drug and dual drug agents. The data of this work suggest that antiplatelets agents may have a role in inhibition of stroke mediated proinflammatory cytokine effects, which may initiate a new aspect of the role of antiplatelets in the treatment of acute ischemic stroke.

Topics: Acute Disease; Adult; Aged; Aspirin; Brain Ischemia; Cells, Cultured; Clopidogrel; Dipyridamole; Female; Humans; In Vitro Techniques; Interleukin-8; Leukocytes; Male; Middle Aged; Piracetam; Platelet Aggregation Inhibitors; Stroke; Ticlopidine; Tumor Necrosis Factor-alpha

Lipopolysaccharide (LPS) and inflammatory cytokines cause activation of sphingomyelinases (SMases) and subsequent hydrolysis of sphingomyelin (SM) to produce a lipid messenger ceramide. The use of SMase inhibitors may offer new therapies for the treatment of the LPS- and cytokines-related inflammatory bowel disease (IBD). We synthesized a series of difluoromethylene analogues of SM (SMAs). Here, we show that LPS efficiently increases the release of IL-8 from HT-29 intestinal epithelial cells by activating both neutral SMase and nuclear factor (NF)-kappaB in the cells. The addition of SMA-7 suppressed neutral SMase-catalyzed ceramide production, NF-kappaB activation, and IL-8 release from HT-29 cells caused by LPS. The results suggest that activation of neutral SMase is an underlying mechanism of LPS-induced release of IL-8 from the intestinal epithelial cells. Ceramide production following LPS-induced SM hydrolysis may trigger the activation of NF-kappaB in nuclei. Oral administration of SMA-7 (60 mg/kg) to mice with 2% dextran sulfate sodium (DSS) in their drinking water, for 21 consecutive days, reduced significantly the severity of colonic injury. This finding suggests a central role for SMase/ceramide signaling in the pathology of DSS-induced colitis in mice. The therapeutic effect of SMA-7 observed in mice may involve the suppression of IL-8 production from intestinal epithelial cells by LPS or other inflammatory cytokines.

Topics: Acute Disease; Administration, Oral; Animals; Cell Line; Ceramides; Colitis; Dextran Sulfate; Interleukin-8; Intestinal Mucosa; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Sphingomyelin Phosphodiesterase; Sphingomyelins

Chemokines have been implicated in the control of leucocyte infiltration in uveitis and in modulating angiogenesis in several ocular conditions. Toxoplasmic retinochoroiditis is a common cause of posterior uveitis. This study aimed to evaluate the serum concentrations of CC and CXC chemokines in patients with acute toxoplasmic retinochoroiditis.. The levels of five chemokines (CCL2, CCL11, CXCL9, CXCL8 and CXCL10) were evaluated in the serum of patients with active toxoplasmic retinochoroiditis (n = 55) and control subjects (n = 40). In a subset of patients (n = 18), a second measure of serum levels of chemokines was performed after the completion of oral treatment with pyrimethamine (25 mg/day), sulphadiazine (1 g, four times per day), folinic acid (7.5 mg/day) and prednisone (initial dose: 1 mg/kg/day) for approximately 30 days.. Patients with toxoplasmic retinochoroiditis, notably those presenting with vasculitis, had increased serum levels of CXCL8 (mean +/- standard error of the mean [SEM] 35.1 +/- 6.5 pg/ml) compared with control subjects (mean +/- SEM 16.0 +/- 2.3 pg/ml; p = 0.01). There were no differences between patients and controls in serum levels of the other chemokines measured. The size of ocular lesions correlated significantly with serum levels of CXCL8 and CXCL9. After treatment, there was a significant reduction in serum levels of CXCL8. Severity of vitreous opacities did not correlate with serum levels of these chemokines.. These data suggest a role for CXCL8 in the inflammatory process of acute toxoplasmic retinochoroiditis. Furthermore, CXCL8 may be a useful marker for patient follow-up.

Topics: Acute Disease; Adult; Anti-Inflammatory Agents; Antiprotozoal Agents; Chorioretinitis; Female; Humans; Interleukin-8; Leucovorin; Male; Optic Disk; Prednisone; Pyrimethamine; Sulfadiazine; Toxoplasmosis, Ocular; Vasculitis; Visual Acuity

To modify the skin window technique for extended analysis of acute inflammatory responses in humans, and demonstrate its applicability for investigating disease.. 15 healthy subjects and 5 Crohn's patients.. Skin windows, created by dermal abrasion, were overlaid for various durations with filter papers saturated in saline, 100 ng/ml muramyl dipeptide (MDP) or 10 microg/ml interleukin-8 (IL-8).. Exuded leukocytes were analyzed by microscopy, immunoblot, DNA-bound transcription factor arrays and RT-PCR. Inflammatory mediators were quantified by ELISA.. Infiltrating leukocytes were predominantly neutrophils. Numerous secreted mediators were detectable. MDP and IL-8 enhanced responses. Many signalling proteins were phosphorylated with differential patterns in Crohn's patients, notably PKC alpha/beta hyperphosphorylation (11.3 +/- 3.1 vs 1.2 +/- 0.9 units, P < 0.02). Activities of 44 transcription factors were detectable, and sufficient RNA isolated for expression analysis of over 400 genes.. The modifications enable broad characterisation of inflammatory responses and administration of exogenous immunomodulators.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Acute Disease; Adjuvants, Immunologic; Case-Control Studies; Cell Movement; Crohn Disease; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Gene Expression Regulation; Humans; Immunologic Factors; Inflammation; Interleukin-8; Leukocytes; Neutrophils; Reverse Transcriptase Polymerase Chain Reaction; Skin; Skin Window Technique; Transcription Factors

Topics: Acute Disease; Bronchiolitis, Viral; C-Reactive Protein; Humans; Infant, Newborn; Inflammation; Interferon-gamma; Interleukin-4; Interleukin-8; Leukocytes; Macrolides; Respiratory Syncytial Virus Infections; Treatment Outcome

The effects of protease-activated receptor-2 (PAR-2) stimulation on inflammation mechanisms of chronic rhinosinusitis (CRS) are still unknown.. PAR-2 receptor expression was investigated by immunohistochemistry and Taqman mRNA analysis in the mucosa of different rhinosinusitis entities. In primary nasal epithelial cell cultures, the function of PAR-2 and its ability to produce CXC, CC chemokines, and IL-6 were measured by calcium mobilization and stimulation tests. Inhibition tests were performed using cortisone, serine protease inhibitors, cysteine protease inhibitors, Pertussis toxin (PTX) and nuclear transcription factor (NF-kappaB) inhibition (BAY 11-7085). Signal transduction pathways were analysed by electromobility shift assays (EMSA) and NF-kappaB binding studies.. The expression of PAR-2 was found to be increased in CRS specimens. The activation of PAR by trypsin or PAR-2-specific activating peptide (AP) caused an increase in cytosolic calcium, as well as the release of the CXC chemokines IL-8 and growth-related oncogene (GRO)-alpha, but not the release of CC chemokines or IL-6. AP-induced CXC chemokine was sensitive to PTX and activation of NF-kappaB was inhibited by BAY11-7085. Furthermore, a serine protease inhibitor significantly inhibited chemokine synthesis stimulated by trypsin and culture supernatants of staphylococci, whereas steroids and cysteine protease inhibitors had little effect.. PAR-2 plays a role in serine protease-mediated regulation - staphylococcal and non-staphylococcal origin - of IL-8 and GRO-alpha in nasal epithelial cells, but not in the regulation of CC chemokines. PAR-2 may therefore be involved in the pathophysiology of CRS and NP at different sites of activation, namely (i) proteases, (ii) the PAR-2 receptor itself or (iii) the application of novel agents that block NF-kappaB/IkappaB-alpha signalling.

Topics: Acute Disease; Adult; Aged; Bacterial Proteins; Calcium; Case-Control Studies; Cells, Cultured; Chemokine CCL11; Chemokine CCL17; Chemokine CCL5; Chemokine CXCL1; Chemokines, CC; Chemokines, CXC; Chronic Disease; Culture Media, Conditioned; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Nasal Mucosa; Nasal Polyps; NF-kappa B; Nitriles; Peptides; Pertussis Toxin; Receptor, PAR-2; Rhinitis; RNA, Messenger; Serine Endopeptidases; Serine Proteinase Inhibitors; Signal Transduction; Sinusitis; Staphylococcus aureus; Sulfones; Trypsin

The relationship between direct count of peripheral blood leucocyte populations and plasma concentrations of IL-6, IL-8, sTNFR-55 and sTNFR-75 during five initial days of acute pancreatitis was studied.. Most significant relationship was found for monocytes, which correlated with sTNFR-55 (R = 0.38, p < 0.05) and sTNFR-75 (R = 0.41, p < 0.05 and R = 0.55, p < 0.01 during 1st and 2nd day, respectively). Later, in days 2, 3 and 4 an interrelation between monocytes and IL-6 (R = 0.49 to R = 0.41, p < 0.01) was observed. Monocytes also correlated with IL-8 in days 2 and 3 (R = 0.41, p < 0.05 and R = 0.43, p < 0.01, respectively). Neutrophil count correlated with IL-6 in days 3 and 4 (R = 0.34, p < 0.05 and R = 0.56, p < 0.01, respectively) and with IL-8 in the 4th day only (R = 0.39, p < 0.05). No significant correlations of lymphocyte, eosinophil and basophil direct counts with cytokines and receptors during the initial 5 days of AP were found.. Observed relationships between monocyte direct counts and plasma cytokine levels reflect monocytes involvement in the development of acute pancreatitis.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Blood Cell Count; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Monocytes; Neutrophils; Pancreatitis; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type II; Tumor Necrosis Factor-alpha

An in vivo rat model of disc degeneration with emphasis on characterizing acute and chronic cytokine production.. To compare the morphologic and proinflammatory response between a single and triple-stab injury in attempts to establish mechanisms of chronic disc inflammation.. The features that distinguish physiologic (asymptomatic) from pathologic (symptomatic) degeneration are unclear. Epidemiologic evidence suggests that cumulative damage and elevated disc cytokine levels may be linked to increased low back pain rates. Although acute injury stimulates a healing response that includes transient cytokine production, repetitive damage may be necessary to trigger the persistent inflammation suspected to underlie chronic pain.. Tail discs were exposed surgically and stabbed with a number 11 blade. During the subsequent acute healing phase, triple-stab discs were percutaneously injured with a 23-gauge needle at day 3 and then again at day 6 after the initial blade incision. Cytokine (IL-1 beta, IL-6, IL-8, and TNF-alpha) production was quantified using enzyme linked immunosorbent assay, and, in addition to MAPK signaling pathways (phosphorylated forms of ERK, JNK, and p38), was localized by immunohistochemistry. Disc architecture was evaluated using histology.. Both single-stab and triple-stab discs degenerated with time, yet degeneration was more severe with repeated injury where nuclear proteoglycan was replaced by disorganized collagen. Four days after single-stab, there was a transient peak in IL-1 beta and IL-8 production that was localized to the wound track and associated granulation tissue. By contrast, triple-stab induced an activated annular fibroblast phenotype (p38 positive) that caused a prolonged, diffuse inflammatory response with elevated levels of TNF-alpha, IL-1 beta, and IL-8 up to 28 days after injury. Disc inflammation was accompanied by reactive changes in the adjacent vertebral marrow spaces that was initially lytic at day 4, becoming sclerotic by day 56.. Our results demonstrate that repeated injury during active healing leads to persistent inflammation and enhanced disc degeneration. These data support the premise that damage accumulation and its associated inflammation may distinguish pathologic from physiologic disc degeneration. In the future, this triple-stab model may be useful to evaluate the efficacy of anti-inflammatory low back pain treatments.

Topics: Acute Disease; Animals; Awards and Prizes; Chronic Disease; Cytokines; Discitis; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Interleukin-1beta; Interleukin-6; Interleukin-8; Intervertebral Disc; JNK Mitogen-Activated Protein Kinases; Low Back Pain; Lymphotoxin-alpha; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Rats; Rats, Sprague-Dawley; Spinal Diseases; Time Factors; Wound Healing; Wounds, Stab

Chemokines are involved in leucocyte chemotaxis. Infiltrating leucocytes play an important role of tissue injury in systemic lupus erythematosus (SLE).. To investigate the role of inflammatory chemokines and their association with interleukin 18 (IL18) in SLE pathogenesis and disease activity.. Plasma concentrations and ex vivo peripheral blood mononuclear cell production of inflammatory chemokines IP-10, RANTES, MIG, MCP-1, TARC, IL8, and GROalpha, and proinflammatory cytokines IL18, IFNgamma, IL2, IL4, and IL10 were assayed in 80 SLE patients with or without renal disease and 40 healthy controls by immunofluorescence flow cytometry and enzyme linked immunosorbent assay.. Plasma IP10, RANTES, MIG, MCP-1, GROalpha, and IL18 concentrations in all SLE patients were higher than in controls, and correlated significantly with SLEDAI score (all p<0.05). In SLE patients without renal disease, IP10, RANTES, MIG, MCP-1, IL8, and IL18 correlated positively with SLEDAI score, while in those with renal derangement, IP10, IL8, IL10, and IL18 correlated with disease activity (all p<0.05). Plasma IL18 concentration correlated positively with IP10, MIG, GROalpha, and IL8 in all SLE patients (all p<0.005). Mitogen induced increases in ex vivo production of IP10, MCP-1, TARC, IFNgamma, IL4, and IL10 were higher in all SLE patients regardless of their difference in disease activity (all p<0.05). Patients with renal disease had an augmented ex vivo release of RANTES.. The correlation of raised plasma concentration and ex vivo production of inflammatory chemokines with disease activity, and their association with IL18, supports the view that chemotaxis of Th1/Th2 lymphocytes and neutrophils is important in SLE pathogenesis.

Topics: Acute Disease; Adult; Analysis of Variance; Case-Control Studies; Cells, Cultured; Chemokine CCL17; Chemokine CCL2; Chemokine CCL5; Chemokine CXCL9; Chemokines; Chemokines, CC; Chemokines, CXC; Female; Humans; Intercellular Signaling Peptides and Proteins; Interferon-gamma; Interleukin-10; Interleukin-18; Interleukin-8; Leukocytes, Mononuclear; Lipopolysaccharides; Lupus Erythematosus, Systemic; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes

Nuclear factor-kappa B (NF-kappaB) is a transcription factor for a wide range of proinflammatory mediators while heat shock factor-1 (HSF-1) transcribes stress proteins that protect against cellular damage. Both are attractive therapeutic targets, undergoing investigation in other acute inflammatory conditions, such as sepsis.. To evaluate the role of the transcription factors NF-kappaB and HSF-1 in human acute pancreatitis and their relationship to cytokine/chemokine production, disease severity and outcome.. Twenty-four patients with acute pancreatitis and 12 healthy controls.. Peripheral blood mononuclear cells were isolated. NF-kappaB and HSF-1 were measured by electrophoretic mobility shift assay. Soluble tumor necrosis factor (TNF) receptor II and interleukin-8 were measured by ELISA. Acute physiology scores (APS), APACHE II scores and final Atlanta designations of severity were also determined.. Systemic NF-kappaB activation occurs in acute pancreatitis compared to healthy controls (P=0.004). However, there was no significant difference between those with mild and severe disease (P=0.685). Systemic activation of HSF-1 was observed in acute pancreatitis compared to healthy controls although this did not reach statistical significance (P=0.053). Activation, however, was greatest in those who had a final Atlanta designation of mild pancreatitis compared to those who had a severe attack of acute pancreatitis (P=0.036). Furthermore, HSF-1 was inversely correlated with acute physiology score (APS; r=-0.49, P=0.019) and APACHE II score (r=-0.47, P=0.026).. Both NF-kappaB and HSF-1 are systemically activated in human acute pancreatitis. HSF-1 activation may protect against severity of pancreatitis.

Topics: Acute Disease; Biomarkers; Cell Nucleus; Chemokines; Cytokines; DNA-Binding Proteins; Heat Shock Transcription Factors; Humans; Interleukin-8; Leukocytes, Mononuclear; NF-kappa B; Pancreatitis; Receptors, Tumor Necrosis Factor, Type II; Reference Values; Transcription Factors

We have reported that peripheral lymphocyte reduction due to apoptosis is linked to the development of subsequent infectious complications in patients with severe acute pancreatitis and that Th1 (helper T cell type 1)/Th2 (helper T cell type 2) balance tends to cause Th1 suppression in experimental severe acute pancreatitis. It has been reported that interleukin (IL)-18 is a cytokine produced from Kupffer cells and activated macrophages, and that IL-18 acts on Th1 cells and in combination with IL-12 strongly induces production of interferon-gamma. However, the role of IL-18 in acute pancreatitis has not yet been fully understood.. Serum IL-18 concentrations were determined by an enzyme-linked immunosorbent assay in 43 patients with acute pancreatitis at the time of admission. The relationships with etiology, pancreatic necrosis, severity, blood biochemical parameters on admission, infection, and organ dysfunction during the clinical course and prognosis were analyzed.. Serum IL-18 levels in patients with acute pancreatitis (656+/- 11pg/ml) were significantly higher than those in healthy volunteers (126+/- pg/ml). Serum IL-18 levels were significantly positively correlated with the Ranson score and Japanese severity score. Among the blood biochemical parameters on admission, base excess and total protein were significantly negatively correlated with serum IL-18 levels. Moreover, the CD4/CD8 rate of lymphocytes, serum IL-6 levels, and serum IL-8 levels were significantly positively correlated with serum IL-18 levels. On day 7 after admission, the CD4/CD8 rate of lymphocytes and the rate of CD4-positive lymphocytes were significantly positively correlated with serum IL-18 levels. Furthermore, serum IL-18 levels in patients with hepatic dysfunction (980+/- 25pg/ml) were significantly higher than those without hepatic dysfunction (464+/- 8pg/ml). Serum IL-18 levels were not related to infection or prognosis. Elevation of serum IL-18 levels continued during 4 weeks after admission.. These results suggest that serum IL-18 levels are significantly elevated and are correlated with severity in patients with acute pancreatitis and that IL-18 may be closely related to helper T cell response and hepatic dysfunction in this disease.

Topics: Acute Disease; Blood Proteins; CD4 Lymphocyte Count; CD4-CD8 Ratio; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hydrogen-Ion Concentration; Interleukin-18; Interleukin-6; Interleukin-8; Male; Middle Aged; Pancreatitis; Severity of Illness Index; T-Lymphocytes, Helper-Inducer

Acute rejection (AR) is an important complication that can occur after lung transplantation and constitutes a risk factor for bronchiolitis obliterans syndrome, which is characterised by a neutrophilic airway inflammation. The specific aim of this study was to investigate the role of interleukin (IL)-17, which promotes chemotaxis of neutrophils by inducing IL-8 production, in AR. Cell differentials, mRNA and protein levels were quantified in bronchoalveolar lavages (BALs) taken from patients at 28 and 90 days after lung transplantation. The patient's rejection status was assessed by transbronchial biopsy. An AR was found in nine out of the 26 patients examined, 28 days after transplantation. The number of BAL neutrophils and lymphocytes were increased in these patients. IL-17 mRNA and protein levels in the BAL were increased in patients with AR. Analysis of BAL obtained at day 90 after transplantation, demonstrated that the increase in IL-17 had disappeared, whereas the increase in neutrophils and lymphocytes persisted. These data showed that interleukin-17 is temporarily upregulated in bronchoalveolar lavage during acute rejection. The number of lymphocytes and neutrophils are increased in bronchoalveolar lavage during acute rejection and may persist up to 2 months after acute rejection. These findings suggest that interleukin-17 is important in the pathophysiology of acute lung rejection.

Topics: Acute Disease; Adult; Biopsy; Bronchoalveolar Lavage Fluid; Bronchoscopy; Chemotaxis, Leukocyte; Female; Gene Expression; Graft Rejection; Humans; Interleukin-17; Interleukin-8; Leukocyte Count; Lung; Lung Transplantation; Male; Middle Aged; Neutrophils; RNA, Messenger

Acute lung injury (ALI) and its extreme manifestation the acute respiratory distress syndrome (ARDS) complicate a wide variety of serious medical and surgical conditions. Thioredoxin is a small ubiquitous thiol protein with redox/inflammation modulatory properties relevant to the pathogenesis of ALI. We therefore investigated whether thioredoxin is raised extracellulary in patients with ALI and whether the extent of any increase is dependent upon the nature of the precipitating insult.. Bronchoalveolar lavage (BAL) fluid and plasma samples were collected from patients with ALI (n=30) and healthy controls (n=18, plasma; n=14, BAL fluid). Lung tissue was harvested from a separate group of patients and controls (n=10). Thioredoxin was measured by ELISA in fluids and by immunohistochemistry in tissue. Interleukin (IL)-8 levels were determined by ELISA. Disease severity was assessed as APACHE II and SOFA scores.. BAL fluid levels of thioredoxin were higher in patients with ALI than in controls (median 61.6 ng/ml (IQR 34.9-132.9) v 16.0 ng/ml (IQR 8.9-25.1), p<0.0001); plasma levels were also significantly higher. When compared with controls, sections of wax embedded lung tissue from patients with ALI showed greater positive staining for thioredoxin in alveolar macrophages and type II epithelial cells. BAL fluid levels of thioredoxin correlated with IL-8 levels in BAL fluid but not with severity of illness scores or mortality. BAL fluid levels of thioredoxin, IL-8, and neutrophils were significantly greater in patients with ALI of pulmonary origin.. Extracellular thioredoxin levels are raised in patients with ALI, particularly of pulmonary origin, and have a significant positive association with IL-8. Extracellular thioredoxin levels could provide a useful indication of inflammation in ALI.

Topics: Acute Disease; Adult; Autopsy; Biopsy; Bronchitis; Bronchoalveolar Lavage Fluid; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Interleukin-8; Male; Middle Aged; Respiratory Distress Syndrome; Thioredoxins

The prognostic importance of interleukin-6 (IL-6), IL-8, and IL-10 in the prediction of acute pancreatitis severity.. Early assessment of severity in acute pancreatitis could help the patients who are at risk of developing complications. Unfortunately, the used prognostic scoring systems generally are only moderately accurate in assessing disease severity.. We studied 117 consecutive patients with a diagnosis of acute pancreatitis admitted to our hospital during the past 2 years. Laboratory parameters and cytokines were analyzed from serum taken routinely on admission. Severity criteria were noted for each patient using Ranson, Glasgow, and APACHE II scoring systems. Local and systemic complications, developed during a follow-up period, were classified by Atlanta criteria.. IL-6 was the only parameter that statistically significantly predicted complicated acute pancreatitis (P<0.05). IL-8 and IL-10 and the 3 prognostic scoring systems used did not properly assess complicated versus noncomplicated acute pancreatitis.. Our prospective study supported the potential importance of IL-6 in the early assessment of complicated acute pancreatitis, but also suggested that pancreatitis classified as complicated in a large number of patients could not be correctly predicted with the Ranson, Glasgow, and APACHE II scoring systems.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; APACHE; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Pancreatitis; Prognosis; Prospective Studies; ROC Curve; Sensitivity and Specificity; Severity of Illness Index

We examined whether epithelial damage is associated with mobilization of neutrophils or eosinophils in the airway lumen during acute exacerbations of paediatric asthma. Aspirated sputum samples were harvested from 65 paediatric patients (mean age 3.4 +/- 0.4 years) during acute exacerbations of asthma. Patients with signs of infection were excluded. The presence of conglomerates of epithelial cells (i.e. "Creola bodies") in the aspirated sputum was utilized as a marker of epithelial damage. Among the paediatric asthma patients, 60% displayed Creola bodies (CrB+: n = 39) in their sputum samples whereas the remaining patients did not (CrB-: n = 26). CrB+ patients displayed more than a 20-fold increase in the concentration of the neutrophil-mobilizing cytokine interleukin (IL)-8 (pg/ml) and of the neutrophil product neutrophil elastase (NE, g/l), respectively, compared with CrB- patients (IL-8: 7468.2 +/- 1953.6 versus 347.9 +/- 72.6, P < 0.01; NE: 2072.4 +/- 419.0 versus 438.5 +/- 125.7, P < 0.01). Even though not statistically significant, a corresponding trend was observed for the relative number of sputum neutrophils. In contrast, the concentration of the eosinophil-mobilizing cytokine IL-5 and the esoinophil product ECP tended to be lower in CrB+ than in CrB- patients (P > 0.05). In conclusion, as indicated by the analysis of aspirated sputum, epithelial damage is associated with a locally enhanced chemotactic signal for and activity of neutrophils, but not eosinophils, during acute exacerbations of paediatric asthma. It remains to be determined whether these indirect signs of neutrophil mobilization in the airway lumen mirror an increased number of neutrophils in the surrounding airway tissue.

Topics: Acute Disease; Asthma; Bradykinin; Child, Preschool; Eosinophil Cationic Protein; Eosinophils; Epithelial Cells; Family Health; Female; Humans; Immunoglobulin E; Infant; Interleukin-5; Interleukin-8; Leukocyte Count; Leukocyte Elastase; Male; Neutrophils; Sputum; Tumor Necrosis Factor-alpha

Recently, sera from children with active Henoch-Schönlein purpura (HSP) have been found to enhance interleukin (IL)-8 production by human umbilical venous endothelial cells (HUVEC). To further determine the possible factor with the ability to enhance endothelial IL-8 production in sera from acute stage of HSP, 10 children with HSP at the acute stage and 10 healthy controls were enrolled. IgA antiendothelial cell antibodies (AECA) were detected by cell-based ELISA. Active sera with or without pretreatment with anti-human IgA antibody, sera of controls, and immunoglobulin A (IgA) derived from sera were used to stimulate the HUVEC. The ability of these factors to enhance endothelial IL-8 production was evaluated. Furthermore, signalling pathways were also assayed by different inhibitors, and confirmed by immunoblotting. Serum levels of IgA AECA in HPS patients at the acute stage were significantly higher than in controls (P < 0.001). The active sera could enhance endothelial IL-8 production (P = 0.004, compared with control sera), and the ability of these sera was mostly abolished when pretreated with fixed anti-human IgA antibody. The supernatant IL-8 levels of endothelial cells stimulated by IgA derived from acute stage of HSP were statistically higher than controls (P < 0.001). PD98059, an inhibitor of ERK phosphorylation, significantly reduced IgA AECA-stimulated endothelial IL-8. IgA AECA also enhanced the phosphorylation of ERK1 with a time-dependent manner. Together with these findings, it is concluded that IgA AECA derived from acute stage of HSP may bind to endothelial and enhance endothelial cells to produce IL-8 via MEK/REK signalling pathway.

Topics: Acute Disease; Autoantibodies; Child; Endothelial Cells; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Humans; IgA Vasculitis; Immunoglobulin A; Interleukin-8; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphorylation; Signal Transduction; Tumor Necrosis Factor-alpha

In an animal model of acute myocardial infarction (AMI), deletion of matrix metalloproteinase (MMP)-9 results in suppression of the development of cardiac rupture. The present study sought to clarify how myocardial MMP-9 activity is related to the pathophysiologies of AMI and cardiac rupture in humans.. Levels of interleukin-8 (IL-8), polymorphonuclear leukocyte (PMN) elastase, monocyte chemotactic protein-1 (MCP-1) and MMP activity were measured in the pericardial fluid obtained from 28 patients with angina pectoris (AP group) and 16 patients with AMI (AMI group) undergoing cardiac surgery. In the AMI group, 5 were complicated with ventricular septal perforation (VSP) and the remaining 11 were not (non-VSP). Levels of IL-8, PMN elastase, MMP-2 and MMP-9 activity were all higher in the AMI group than in the AP group. In the AMI group, all levels other than MMP-2 activity were further elevated in cases with VSP compared with those in the non-VSP group. There was no significant difference in MCP-1 among the groups. Markers of neutrophil activation in the infarcted cardiac tissue seem to be elevated in AMI. Highly elevated levels of MMP-9 activity, which may be derived from neutrophils, and PMN elastase may be related to the pathophysiology of VSP or cardiac rupture in AMI.

Topics: Acute Disease; Aged; Animals; Biomarkers; Chemokine CCL2; Disease Models, Animal; Female; Gene Deletion; Humans; Interleukin-8; Leukocyte Elastase; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Myocardial Infarction; Neutrophil Activation; Neutrophils; Pericardium; Ventricular Septal Rupture

Early identification of the pathogen causing acute gastroenteritis in children helps the physicians managing the disease and prevents unnecessary antibiotic treatment. C-reactive protein (CRP), interleukin (IL) 6 and IL-8 play a major role in immune responses and have been studied in a large number of infectious and noninfectious inflammatory diseases. The purpose of this study was to determine the serum IL-6 and IL-8 concentrations early in the course of acute gastroenteritis to see if these cytokines were useful diagnostic markers in differentiating viral from bacterial gastroenteritis.. Interleukin 6, IL-8 and CRP were measured in 18 patients with bacterial gastroenteritis, 21 patients with viral gastroenteritis and 17 healthy children.. Interleukin 6 and CRP concentrations in patients with bacterial gastroenteritis were significantly higher than those in patients with viral gastroenteritis and healthy controls (P < 0.001). IL-8 concentrations in patients with viral and bacterial gastroenteritis were both increased and were not statistically different. IL-6 and IL-8 levels had diagnostic sensitivities of 79% and 50% and specificities of 86% and 67%, respectively. The combination of IL-6 and CRP had a sensitivity of 94%, specificity of 71%, a positive predictive value of 74% and a negative predictive value of 93.75%.. Serum IL-6 may be a useful marker for early differentiation of viral and bacterial gastroenteritis in children, especially in combination with CRP.

Topics: Acute Disease; Biomarkers; C-Reactive Protein; Case-Control Studies; Child, Preschool; Dysentery, Bacillary; Enzyme-Linked Immunosorbent Assay; Female; Gastroenteritis; Humans; Infant; Interleukin-6; Interleukin-8; Male; Rotavirus Infections; Salmonella Infections; Sensitivity and Specificity; Yersinia Infections

To evaluate the relationship between leptin and systemic inflammation in acute pancreatitis.. Consecutive patients with acute pancreatitis were included. Body mass index and serum samples were obtained at admission. Leptin, TNF-alpha, IL-6, -8 and -10 levels were determined by ELISA. Severity was defined according to Atlanta criteria.. Fifty-two (29 females) patients were studied. Overall body mass index was similar between mild and severe cases, although women with severe pancreatitis had lower body mass index (P = 0.04) and men showed higher body mass index (P = 0.05). No difference was found in leptin levels regarding the severity of pancreatitis, but higher levels tended to appear in male patients with increased body mass index and severe pancreatitis (P = 0.1). A multivariate analysis showed no association between leptin levels and severity. The strongest cytokine associated with severity was IL-6. Correlations of leptin with another cytokines only showed a trend for IL-8 (P = 0.058).. High body mass index was associated with severity only in males, which may be related to android fat distribution. Serum leptin seems not to play a role on the systemic inflammatory response in acute pancreatitis and its association with severe outcome in males might represent a marker of increased adiposity.

Topics: Acute Disease; Adiposity; Adult; Body Mass Index; Disease Progression; Female; Humans; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity; Pancreatitis; Prognosis; Severity of Illness Index; Sex Characteristics; Tumor Necrosis Factor-alpha

Opinions about early endoscopic sphincterotomy and time of laparoscopic cholecystectomy in acute biliary pancreatitis are still controversial. Some authors reserved this procedure only for cases in which the stones were visualized during ERCP or patients had clinical symptoms of acute cholangitis. The aim was the assessment of the dynamic of changes of proinflammatory cytokines and white blood cells in time in patients with acute biliary pancreatitis after performed endoscopic sphincterotomy and laparoscopic cholecystectomy.. We enrolled 43 consecutive patients with clinically diagnosed mild forms of acute biliary pancreatitis. All were treated by early endoscopic sphincterotomy and laparoscopic cholecystectomy performed during the first 48 hours after admission. The course of the disease was monitored by measurement of the level of proinflammatory cytokines.. Marked decrease of the level of proinflammatory interleukins within 24 hours after endoscopic sphincterotomy was observed. Mean values of IL-6 and IL-8 were statistically lower immidiately after this procedure (p < 0.001). Subsequent decrease was achieved after laparoscopic cholecystectomy. The mean values of TNF-alpha and IL-12p40 were relatively constant throughout the study period.. All patients suffering from mild acute biliary pancreatitis should be treated by using minimally invasive procedures. However, such a only treatment should be reserved for experienced centers.

Topics: Acute Disease; Biliary Tract Diseases; Cholecystectomy, Laparoscopic; Humans; Interleukin-12 Subunit p40; Interleukin-6; Interleukin-8; Leukocyte Count; Minimally Invasive Surgical Procedures; Pancreatitis; Sphincterotomy, Endoscopic; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

To observe the effect of resveratrol on nuclear factor Kappa-B (NF-kappaB) activation and the inflammatory response in sodium taurocholate-induced pancreatitis in rats.. Seventy-two male SD rats were randomly divided into three groups: sham operation group (control), severe acute pancreatitis (SAP) group, and severe acute pancreatitis group treated with resveratrol (RES). A SAP model was established by injecting 4% sodium taurocholate 1 mL/kg through puncturing the pancreatic duct. In Res group, Res was given at 30 mg/kg b.m. intraperitoneally after the SAP model was successfully established. Eight animals from each group were sacrificed at 3, 6 and 12 h after modeling. The expression of NF-kappaB activation of pancreas was detected by immunohistochemical staining, whereas the levels of TNF-alpha and IL-8 in pancreatic tissues were estimated by radioimmunoassay. The pathological changes of pancreas and lungs were examined microscopically.. Much less hyperemia, edema, dust-colored necrotic focus and soaps were noticed in pancreas in RES group than in SAP group. In RES group, hemorrhage, exudates and infiltration of inflammatory cells in pancreas and interstitial edema, destruction of alveolar wall in lung were significantly less than in SAP group. In the SAP group, the activation of NF-kappaB in pancreatic tissues was enhanced significantly at any measure point compared with control group (64.23+/-10.72% vs 2.56+/-0.65%, 55.86+/-11.34% vs 2.32+/-0.42%, 36.23+/-2.30% vs 2.40+/-0.36%,P<0.01), TNF-alpha,IL-8 were also increased and reached their peak at 6 h and then declined. The activation of NF-kappaB and the levels of TNF-alpha and IL-8 in RES group were significantly lower than those in SAP group (P<0.01): activation (52.63+/-9.45% vs 64.23+/-10.72%, 40.52+/-8.40% vs 55.86+/-11.34%, 29.83+/-5.37% vs 36.23+/-2.30%), TNF-alpha (132.76+/-15.68 pg/mL vs 158.36+/-12.58 pg/mL, 220.32+/-23.57 pg/mL vs 247.67+/- 11.62 pg/mL, 175.68+/-18.43 pg/mL vs 197.35+/-12.57 pg/mL) and IL-8 (0.62+/-0.21 microg/L vs 0.83+/-0.10 microg/L, 1.10+/-0.124 microg/L vs 1.32+/-0.18 microg/L, 0.98+/-0.16 microg/L vs 1.27+/-0.23 microg/L).. The activation of NF-kappaB is involved in the inflammatory response of rats with SAP. Resveratrol could effectively inhibit the expression of NF-kappaB activation, alleviate the severity of SAP through its anti-inflammatory effects and regulate the inflammatory mediators.

Topics: Acute Disease; Animals; Antioxidants; Cholagogues and Choleretics; Disease Models, Animal; Interleukin-8; Male; NF-kappa B; Pancreas; Pancreatitis; Rats; Rats, Sprague-Dawley; Resveratrol; Severity of Illness Index; Stilbenes; Taurocholic Acid; Tumor Necrosis Factor-alpha

Interleukin 18 (IL-18) is primarily a macrophage-derived, pro-inflammatory cytokine. As macrophages can act as effector cells in acute rejection, we examined the role of IL-18 in a rat model of acute renal allograft rejection.. Life-sustaining orthotopic DA to Lewis allograft and Lewis-Lewis isograft kidney transplants were performed. In the same model, macrophage-depleted animals, achieved with liposomal-clodronate therapy, were also studied. Macrophage (ED1+) accumulation and IL-18 expression was assessed by immunohistochemistry. CD11b+ cells (macrophages) were isolated from kidney and spleen by micro beads. Real-time PCR was used to assess IL-18 and INF-gamma mRNA expression in tissue and cell isolates.. Allografts, but not isografts, developed severe tubulo-interstitial damage and increased serum creatinine by day 5 (P<0.001). Immunohistochemistry revealed a greater ED1+ cell accumulation in day 5 allografts compared with isografts (P<0.001). IL-18 mRNA expression was increased 3-fold in allografts compared to isografts (P<0.001). Accordingly, IL-18 protein was increased in allografts (P<0.001), and was predominantly expressed by ED1+ macrophages. CD11b+ macrophages isolated from allografts had a 6-fold upregulation of IL-18 mRNA expression compared to isograft macrophages (P<0.001). Macrophage depletion resulted in a marked attenuation of allograft rejection, ED1+ and IL-18+ cells were significantly reduced (P<0.05) as was IL-18 mRNA expression (29.28+/-2.85 vs 62.48+/-3.05, P<0.001). INF-gamma mRNA expression (P<0.01) and iNOS (P<0.001) production were also significantly reduced in the macrophage-depleted animals.. This study demonstrates that IL-18 is significantly increased during acute rejection and is principally produced by intra-graft macrophages. We hypothesize that IL-18 upregulation may be an important macrophage effector mechanism during the acute rejection process.

Topics: Acute Disease; Animals; Graft Rejection; Interleukin-8; Kidney Transplantation; Macrophages; Male; Rats; Rats, Inbred Lew

Septic acute lung injury (ALI) causes high morbidity and mortality in intensive care service as a result of biotrauma and dysfunction in the lungs and other organ systems. We hypothesized that surfactant and/or inhaled nitric oxide (iNO) may have different effects in modulation of inflammatory injury in septic ALI. Twenty-four healthy, 6-9 kg piglets were anesthetized, and intraperitoneally injected with Escherichia coli, followed by a low tidal volume ventilation until sepsis and ALI developed within 4-6 h. They were then randomly treated in groups (n=6 each) as: control (C), inhaled NO at 10 ppm (NO), surfactant at 100mg/kg (Surf), or both surfactant and iNO (SNO). A normal control group (N) was sham-injected and similarly ventilated. Over the 24 h of treatment period, both Surf, and SNO groups had significantly improved PaO2/FiO2, dynamic compliance and resistance of respiratory system. At 24h, the best alveolar aeration and least protein leakage, the lowest wet-to-dry lung weight ratio and lung injury score were found in SNO. Activity of nuclear factor kappa B (NF-kappaB) and myeloperoxidase, interleukin 8 mRNA expression and melondialdehyde were significantly increased, and IL-10 mRNA decreased, in lung tissue of the C group, but were significantly altered in the SNO group, and moderately altered in either NO or Surf group. We conclude that the effects of lung protection by surfactant and/or iNO in this model may be different in modulation of inflammatory cytokine mRNA expression and activity of NF-kappaB, and iNO did not have adverse effects.

Topics: Acute Disease; Administration, Inhalation; Analysis of Variance; Animals; Bronchoalveolar Lavage Fluid; Electrophoretic Mobility Shift Assay; Escherichia coli Infections; Fibroblast Growth Factor 7; Interleukin-10; Interleukin-8; Lung; Male; Malondialdehyde; Methemoglobin; NF-kappa B; Nitrates; Nitric Oxide; Nitrites; Oligonucleotide Probes; Peroxidase; Pneumonia; Protein Binding; Pulmonary Surfactants; Pulmonary Ventilation; Respiratory Insufficiency; RNA, Messenger; Swine

Airway infection with Haemophilus influenzae causes airway inflammation, and isolation of new strains of this bacteria is associated with increased risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD).. To determine whether strains of H. influenzae associated with exacerbations cause more inflammation than strains that colonize the airways of patients with COPD.. Exacerbation strains of H. influenzae were isolated from patients during exacerbation of clinical symptoms with subsequent development of a homologous serum antibody response and were compared with colonization strains that were not associated with symptom worsening or an antibody response. Bacterial strains were compared using an in vivo mouse model of airway infection and in vitro cell culture model of bacterial adherence and defense gene and signaling pathway activation in primary human airway epithelial cells.. H. influenzae associated with exacerbations caused more airway neutrophil recruitment compared with colonization strains in the mouse model of airway bacterial infection. Furthermore, exacerbation strains adhered to epithelial cells in significantly higher numbers and induced more interleukin-8 release after interaction with airway epithelial cells. This effect was likely mediated by increased activation of the nuclear factor-kappaB and p38 mitogen-activated protein kinase signaling pathways.. The results indicate that H. influenzae strains isolated from patients during COPD exacerbations often induce more airway inflammation and likely have differences in virulence compared with colonizing strains. These findings support the concept that bacteria infecting the airway during COPD exacerbations mediate increased airway inflammation and contribute to decreased airway function.

Topics: Acute Disease; Aged; Animals; Bacterial Adhesion; Female; Haemophilus Infections; Haemophilus influenzae; Humans; In Vitro Techniques; Interleukin-8; Longitudinal Studies; Male; Mice; Middle Aged; Neutrophils; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Pneumonia; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa

The predominant problems associated with peritoneal dialysis (PD) are ultrafiltration failure and peritonitis. PD maintains a state of intraperitoneal inflammation that affects the structure and function of the peritoneal membrane, potentially impairing ultrafiltration efficiency. Paradoxically, some PD fluids also have anti-inflammatory properties that may compromise the immune defense against peritonitis. This anti-inflammatory feature is mostly due to the glucose degradation products (GDPs), formed during heat-sterilization and storage of PD fluids. The main purpose of the present thesis was to study regulatory mechanisms behind the acute intraperitoneal inflammatory response in PD in the presence and absence of experimental peritonitis. Rats were exposed to a single dose of heat- or filter sterilized PD fluids either as an i.p. injection or as an infusion through an indwelling catheter, with or without supplementations, or pretreatment of the animals. The dwell fluid was analyzed zero, two and four hours later concerning activation of the complement and coagulation cascades, neutrophil recruitment and respiratory burst, ultrafiltration volumes, cytokine-induced neutrophil chemoattractant (CINC-1), rat mast cell protease 2 (RMCP-2), glucose, urea and histamine concentrations and ex vivo/in vitro intraperitoneal chemotactic activity. Exposure to filter sterilized PD fluid alone induced intraperitoneal complement activation and coagulation, neutrophil recruitment and increased the levels of CINC-1 during the dwell. Intraperitoneal concentrations of the mast cell markers histamine and RMCP-2 changed little during the dwells and did not indicate mast cell activation. Low molecular weight heparin (LMWH) and C5 blockade improved ultrafiltration. Pretreatment with cobra venom factor, known decomplementing agent, blocked the CINC-1 release and the neutrophil recruitment and improved ultrafiltration. In combination with experimental peritonitis, heat sterilized PD fluid compared to filter sterilized, inhibited the CINC-1 release and the recruitment of neutrophils to the peritoneal cavity without affecting the intraperitoneal complement activation. The results of the present thesis indicate that addition of LMWH to the PD fluid improves ultrafiltration, probably by blocking C5a activity. C5 blockade seems to improve ultrafiltration by a mechanism that involves a reduction in glucose transport, possibly by reducing C5 induced vasodilatation. Complement activation

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Anticoagulants; Blood Coagulation; Chemokine CXCL1; Chemokines, CXC; Complement Activation; Complement C5a; Dialysis Solutions; Heparin, Low-Molecular-Weight; Intercellular Signaling Peptides and Proteins; Interleukin-8; Male; Mast Cells; Neutrophil Infiltration; Peritoneal Dialysis; Peritonitis; Rats; Rats, Sprague-Dawley; Respiratory Burst

To investigate the effects of antipyretic and purgative herbs on intestinal mucosal barrier and inflammatory response in the treatment of acute cholangitis.. Sixty SD rats were randomly divided into group A (untreated group, acute cholangitis was induced, n=20), group B (treatment group, acute cholangitis was induced and treated with antipyretic and purgative herbs, n=20) and group C (sham operation group, n=20). At the third or fifth day after operation, the rats were sacrificed and sampled. The serum endotoxin, cytokines and inflammatory mediators were tested and the numbers of labeled bacteria in the liver, spleen and mesenteric lymph nodes translocated from the gut were assayed.. As compared with group A, the serum content of endotoxin, IL-6, IL-8, TNF-alpha, CRP and NO was significantly lower and that of IL-2 was significantly higher, and the translocated numbers of labeled bacteria from gut were reduced in both group B and group C (P<0.01).. Antipyretic and purgative herbs can play therapeutic roles in the treatment of acute biliary tract infections, including the protection of intestinal mucosal barrier from bacterial translocation, reduction of serum endotoxin content and regulation of inflammatory response.

Topics: Acute Disease; Animals; Bacterial Translocation; Cholangitis; Drugs, Chinese Herbal; Escherichia coli; Interleukin-6; Interleukin-8; Intestinal Mucosa; Phytotherapy; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Acute lung injury is a common complication in patients with extensive burns in which the burned area exceeds 30% of the total body surface area (TBSA). This study was undertaken to evaluate the effect of Ligustrazine on burn-induced lung injury as well as the release of interleukin-8 (IL-8) in rats to characterize the role of Ligustrazine and IL-8 in lung injury after burn trauma. Sprague-dawley rats were divided into three groups: (1) sham group, rats who underwent sham burn; (2) control group, rats given third-degree burns over 30% TBSA and lactated Ringer solution for resuscitation; and (3) Ligustrazine group, rats given burn injury and lactated Ringer's solution with Ligustrazine inside for resuscitation. Pulmonary injury was assessed at 24 h by pulmonary capillary permeability determined with fluorescein isothiocyanate-labeled albumin and lung histologic analysis, and lung myeloperoxidase (MPO) activity as well as lung wet/dry weight ratio. The IL-8 levels were measured in serum by enzyme-linked immunosorbent assay. These studies showed that burn trauma results in increased pulmonary leakage permeability and lung wet/dry ratio, elevated serum IL-8 levels and MPO activity, and worsened histologic condition. Ligustrazine inhibited these changes, prevented burn-mediated lung injury, and the production of IL-8. This will likely provide further evidence for ligustrazine as a therapeutic strategy in burn-induced lung injury.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Burns; Capillary Permeability; Interleukin-8; Lung; Male; Models, Animal; Peroxidase; Pyrazines; Random Allocation; Rats; Rats, Wistar; Respiratory Distress Syndrome

In this study, we measured the levels of eosinophil cationic protein (ECP) and interleukin (IL)-8 in bronchoalveolar lavage (BAL) fluid from patients with acute asthma and acute bronchiolitis, to determine any similarities or dissimilarities in the profiles of these biochemical markers in the two diseases.. BAL fluids were obtained from children with acute asthma (n=16), infants with acute bronchiolitis caused by respiratory syncytial virus (n=18), and control subjects (n=14). Children with asthma were selected to be free of viral infection. BAL cell counts and differentials were determined, and ECP and IL-8 levels were measured by radioimmunoassay and ELISA, respectively.. ECP levels in BAL fluids were significantly higher in the asthma group than in the bronchiolitis (P<0.01) or control (P<0.0001) groups. However, IL-8 levels were significantly higher in the bronchiolitis group than in the asthma (P<0.01) or control (P<0.001) groups. IL-8 levels in the asthma group and ECP levels in the bronchiolitis group were similar to those of the control group.. This difference in profiles of ECP and IL-8 in acute asthma and acute bronchiolitis, together with a different inflammatory cell pattern, suggests that the nature of the inflammatory process within the lower respiratory tract may be distinctive in these two diseases.

Topics: Acute Disease; Asthma; Bronchiolitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Child, Preschool; Eosinophil Cationic Protein; Eosinophils; Female; Humans; Interleukin-8; Macrophages; Male; Neutrophils

To investigate the role of macrophage migration inhibitory factor (MIF) and its downstream cytokine cascade in necrotizing enterocolitis (NEC).. The expression of MIF mRNA and protein in NEC guts was assayed by in situ hybridization and immunohistochemistry, respectively. Concentrations of MIF, interleukin (IL)-6 and IL-8 in the serum and in the supernatant of macrophage cultures were examined by ELISA. Increased expression of MIF mRNA and protein was observed in the NEC guts, mainly in the infiltrating macrophages in the mucosa and submucosal layers. Up-regulation of MIF was associated with the accumulation of macrophages and T cells. In addition, serum levels of MIF, IL-6 and IL-8 in NEC patients during the acute stage of the disease were significantly increased. The expression of MIF decreased both locally and systemically after the disease was resolved. MIF was also found to increase the secretion of IL-6 and IL-8 by macrophages isolated from healthy individuals in vitro in NEC.. MIF acts by stimulating macrophage production of IL-6 and IL-8. This further aggravates the inflammatory process by increasing the infiltration of neutrophils and activating inflammatory cells. The results of this study suggest that MIF plays an important role in the pathogenesis of NEC and may serve as a target for therapeutic intervention in NEC.

Topics: Acute Disease; Cells, Cultured; Culture Media, Conditioned; Enterocolitis, Necrotizing; Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; In Situ Hybridization; Infant, Newborn; Interleukin-6; Interleukin-8; Macrophage Migration-Inhibitory Factors; Macrophages; RNA, Messenger; Up-Regulation

Oral lichen planus (OLP) is a T-cell-mediated inflammatory disease. Interleukin (IL)-8 is a pro-inflammatory cytokine of host response to injury and inflammation.. To investigate whether serum IL-8 level was a more sensitive marker than serum IL-6 level in monitoring the disease activity of OLP and to assess whether IL-8 was a useful serum marker in evaluating the therapeutic effects of levamisole on OLP patients.. In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 and IL-8 in 158 patients with OLP, nine patients with traumatic ulcers (TU) and 54 normal control subjects. Some OLP patients with the serum IL-6 or IL-8 levels higher than the upper limit of normal serum concentration were treated with levamisole for 0.5-6.0 months and their serum IL-6 and IL-8 levels were measured after treatment.. We found that 28% (44 of 158) OLP, 28% (40 of 142) erosive OLP (EOLP), and 25% (four of 16) nonerosive OLP (NEOLP) patients had a serum IL-6 level greater than the upper normal limit of 4.7 pg mL(-1). In contrast, 63% (99 of 158) OLP, 63% (90 of 142) EOLP and 56% (nine of 16) NEOLP patients had a serum IL-8 level greater than the upper normal limit of 8.7 pg mL(-1). In some OLP patients with the serum IL-6 or IL-8 levels higher than the upper limit of normal serum concentration, treatment with levamisole for a period of 0.5-6.0 months could significantly reduce the mean serum IL-6 level from 14.3 +/- 1.9 pg mL(-1) to 3.2 +/- 0.6 pg mL(-1) (P < 0.001) and could significantly reduce the mean serum IL-8 level from 95.8 +/- 17.1 pg mL(-1) to 14.8 +/- 5.8 pg mL(-1) (P < 0.001).. Because measurement of the serum IL-8 level can detect more OLP patients with an abnormal serum level than measurement of the serum IL-6 level (63% vs. 28%), we conclude that serum IL-8 level is a more sensitive marker than serum IL-6 level in monitoring the disease activity of OLP. Levamisole can modulate both the serum IL-6 and IL-8 levels in OLP patients. IL-8, like IL-6, is also a useful serum marker in evaluating the therapeutic effects of levamisole on OLP patients.

Topics: Acute Disease; Adult; Aged; Analysis of Variance; Biomarkers; Female; Humans; Immunologic Factors; Interleukin-6; Interleukin-8; Levamisole; Lichen Planus, Oral; Male; Middle Aged; Mouth Mucosa; Sensitivity and Specificity

The aim of this study was to determine whether the regulatory immune response (interleukin (IL)-10 response) differed between children hospitalized with acute respiratory infections and wheezing.. Infants with signs and symptoms of acute viral respiratory infection, admitted during winter 2000 to Princess Margaret Hospital for Children, Perth, WA, Australia, were enrolled in this study. Nasopharyngeal aspirates were collected in the first 48 h of admission. Total cell count and differential cell counts were assessed. Samples were tested for the presence of respiratory viruses. The concentrations of the anti-inflammatory cytokine IL-10, and pro-inflammatory cytokines IL-8, interferon-gamma, and IL-11 were determined by ELISA.. Children with acute bronchiolitis (AB; n = 36), recurrent wheeze (RW; n = 17) and upper respiratory infection (URI; n = 18) were enrolled. Respitory syncytial virus was the most commonly detected virus in all groups. IL-10 concentrations were significantly increased in AB (median, 0.019 ng/mL) when compared to URI (median, 0.006 ng/mL) or to RW (median, 0.007 ng/mL; P < 0.05). Neutrophils were the predominant cells in the cytological analysis in all subjects.. These data argue that host-response factors are important in determining the clinical phenotype, independent of the causative virus.

Topics: Acute Disease; Biomarkers; Cell Count; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Inpatients; Interferon-gamma; Interleukin-10; Interleukin-11; Interleukin-8; Male; Nasal Lavage Fluid; Nasal Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Retrospective Studies; Severity of Illness Index

Pulmonary intravascular macrophages (PIMs) are present in ruminants and horses. These species are highly sensitive to acute lung inflammation compared with non-PIM-containing species such as rats and humans. There is evidence that rats and humans may also recruit PIMs under certain conditions. We investigated precise contributions of PIMs to acute lung inflammation in a calf model. First, PIMs were recognized with a combination of in vivo phagocytic tracer Monastral blue and postembedding immunohistology with anti-CD68 monoclonal antibody. Second, gadolinium chloride depleted PIMs within 48 h of treatment (P < 0.05). Finally, PIMs contain TNF-alpha, and their depletion reduces cells positive for IL-8 (P < 0.05) and TNF-alpha (P < 0.05) and histopathological signs of acute lung inflammation in calves infected with Mannheimia hemolytica. The majority of IL-8-positive inflammatory cells in lung septa of infected calves were platelets. Platelets from normal cattle contained preformed IL-8 that was released upon in vitro exposure to thrombin (P < 0.05). These novel data show that PIMs, as the source of TNF-alpha, promote recruitment of inflammatory cells including IL-8-containing platelets to stimulate acute inflammation and pathology in lungs. These data may also be relevant to humans due to our ability to recruit PIMs.

Topics: Acute Disease; Animals; Blood Platelets; Cattle; Interleukin-8; Leukocyte Count; Macrophages, Alveolar; Male; Mannheimia haemolytica; Pasteurellaceae Infections; Pneumonia; Tumor Necrosis Factor-alpha

Previously, we have reported marked pulmonary inflammation in infants who develop chronic lung disease of prematurity. We revisited these infants who did not have clinical or laboratory evidence of infection and searched for Ureaplasma urealyticum, group B streptococci, and other microbes by reverse transcription-PCR performed on RNA extracted from 93 bronchoalveolar lavage samples. From infants ventilated for respiratory distress syndrome, 6 (gestation, 28 wk; birthweight, 880 g) were positive for U. urealyticum and 11 (25 wk, 800 g) were negative. Five (83%) positive and four (36%) negative infants developed chronic lung disease. Each infant was colonized with either biovar 1 or biovar 2 but not both. U. urealyticum was very weakly detectable in two infants on d 1 but was detected in five of six infants at d 10. Furthermore, pulmonary neutrophils, alveolar macrophages, soluble intercellular adhesion molecule-1, and IL-1beta on d 10 and IL-6 and IL-8 at d 1 were significantly increased in the positive group. A variety of organisms were identified in six samples between 14 and 21 d of age, but all samples were negative for group B streptococci. Our data suggest that U. urealyticum colonization is associated with the development of pulmonary inflammation in infants who subsequently develop chronic lung disease.

Topics: Acute Disease; Bronchoalveolar Lavage Fluid; Bronchopulmonary Dysplasia; Chronic Disease; Humans; Infant, Newborn; Infant, Premature; Interleukin-1; Interleukin-6; Interleukin-8; Pneumonia; Risk Factors; RNA, Bacterial; RNA, Ribosomal; Ureaplasma Infections; Ureaplasma urealyticum

The evolution and the relationship between inflammatory and renal-injury markers in women with acute uncomplicated pyelonephritis under antimicrobial therapy were investigated in a prospective study. Markers were measured before and 6 and 24 h after the intravenous administration of 1 g of ceftriaxone. Before treatment, the median levels of all markers except the serum creatinine levels were high. Twenty-four hours after the onset of antibiotic treatment, the C-reactive protein (CRP) level continued to be high, while the serum interleukin-6 (IL-6) levels and the urine IL-6, IL-8, albumin, and immunoglobulin G (IgG) levels decreased significantly. In contrast, serum creatinine and tumor necrosis factor alpha levels and urine N-acetyl-beta-glucosaminidase, alpha1-microglobulin, and beta2-microglobulin levels did not change over time. There was a significant correlation between IL-6 and IL-8 levels and urine albumin and IgG levels (urine albumin and IgG levels are glomerular and urinary tract-injury markers) as well as between serum CRP levels and the levels of the tubular-injury markers. In women with acute pyelonephritis, appropriate antibiotic treatment rapidly decreases serum IL-6 levels and urine IL-6 and IL-8 levels, which correlate well with urine albumin and IgG levels.

Topics: Acute Disease; Adult; Aged; Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Ceftriaxone; Escherichia coli Infections; Female; Humans; Immunoglobulin G; Inflammation Mediators; Interleukin-6; Interleukin-8; Kidney; Middle Aged; Prospective Studies; Pyelonephritis

The complexity of acute and chronic inflammatory processes may either lead to benign prostate hyperplasia (BPH) and/or prostate cancer. Obviously, various tissue cells are activated by chemokines via different chemotaxin receptors which then trigger subsequent processes in angiogenesis, cellular growth, and extravasation as well as neoplasia.. Using the surgically obtained tissue of patients (n = 36) with BPH or prostate carcinoma (PCA), we studied among others the expression of chemokines (Rantes, IL-8), chemotaxin receptors (CXCR-3 and -4, CCR-3, CCR-5), of matrixmetalloproteinases (MMP-2 and 9), of Toll-like (TL) receptors 1, 2, 3, 4, 5, 7, and 9 and of the inducible cyclooxygenase-2 (cox-2) by RT-PCR. Further support for the different properties of tissue from PCA was obtained using two different PCA cell lines (PC3 = androgen resistant cell) or LNCAP cells (androgen sensitive) with emphasis on IL-8, Il-6, and PGE(2) release. Cell lines were stimulated with either the tumor necrosis factor-alpha (TNF-alpha) and lipopolysacharide (LPS) over time. In addition to cytokine release, the quantification of mRNA by lightcycler for cox-2, IL-6, and IL-8 was performed on these cell lines.. Remarkable differences in expression were obtained by RT-PCR when BPH tissue versus PCA was analyzed. Expression of CXCR-1 after incubation with LPS and TNF-alpha showed time-dependent differences for androgen-sensitive LNCAP as compared to androgen-resistant PC-3 cells. TNF-alpha incubation leads to a time-dependent induction of cox-2 expression unlike to activation with LPS. Differences with regard to cox-2, IL-6, and IL-8 expression were seen by quantitative lightcycler analysis. Significant differences were also observed when TL receptors 4, 5, 7, and 9 were analyzed which were significantly expressed in BPH- as compared to PCA-tissue.. Our data clearly demonstrate that various inflammatory and cell biological cascades are involved which either lead to BPH or can be linked to the development of PCA. The exact cell biological mechanisms may provide novel therapeutic options in the treatment of both diseases.

Topics: Acute Disease; Aged; Aged, 80 and over; Cell Transformation, Neoplastic; Chemotactic Factors; Chronic Disease; Cyclooxygenase 2; Cytokines; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Interleukin-6; Interleukin-8; Isoenzymes; Lipopolysaccharides; Male; Membrane Proteins; Middle Aged; Neovascularization, Pathologic; Prostaglandin-Endoperoxide Synthases; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Interleukin-8A; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

This study was undertaken to clarify the effects of propofol on endotoxin-induced acute lung injury. Rabbits were randomly assigned to one of four groups. Each group received intravenous infusion of saline only, saline and Escherichia coli endotoxin, propofol (1 mg/kg bolus, then 5 mg/kg/hr) and endotoxin, or propofol (4 mg/kg bolus, then 20 mg/kg/hr) and endotoxin respectively. Infusion of saline or propofol was started 0.5 hr before the infusion of saline or endotoxin, and continued for 6 hr thereafter. The lungs of rabbits were ventilated with 40% oxygen. Mean blood pressure, heart rate, arterial oxygen tension (PaO2), and peripheral blood leukocyte and platelet count were recorded. The wet/dry (W/D) weight ratio of lung and lung injury score were measured, and analysis of bronchoalveolar lavage fluid (BALF) was done. Endotoxin decreased PaO2, and peripheral blood leukocyte and platelet count. And it increased W/D ratio of lung, lung injury score and leukocyte count, percentage of PMN cells, concentration of albumin, thromboxane B2 and IL-8 in BALF. Propofol attenuated all these changes except the leukocyte count in peripheral blood. In conclusion, propofol attenuated endotoxin-induced acute lung injury in rabbits mainly by inhibiting neutrophil and IL-8 responses, which may play a central role in sepsis-related lung injury.

Topics: Acute Disease; Albumins; Anesthetics, Intravenous; Animals; Blood Platelets; Blood Pressure; Bronchoalveolar Lavage Fluid; Endotoxins; Escherichia coli; Free Radical Scavengers; Interleukin-8; Leukocytes; Lung; Lung Injury; Male; Organ Size; Oxygen; Propofol; Rabbits; Sepsis; Sodium Chloride; Thromboxane B2; Time Factors

Acute pancreatitis after posterior spinal fusion in children is associated with high intraoperative blood loss. Inflammation, oxidative stress, and pancreatitis markers were assessed during this period. Five of the 17 patients studied developed acute pancreatitis 3-7 days after surgery. Intraoperative blood loss (4850 +/- 2315 vs 1322 +/- 617 ml) and peak tumor necrosis factor alpha levels (15.29 +/- 5.3 vs 8.27 +/- 4.6 pg/ml) in the immediate postoperative period were significantly higher in these five patients than in controls, respectively. No differences were noted in serum interleukin 8, interleukin 6, pancreatis-associated protein, or urine malondialdehyde levels. Urine trypsin-associated peptide, elevated initially in all patients, was significantly higher in the acute pancreatitis group at diagnosis. Length of stay was significantly longer in the acute pancreatitis group. Greater blood loss and peak tumor necrosis factor alpha are associated with subsequent risk of acute pancreatitis, suggesting a role of ischemia-reperfusion injury.

Topics: Acute Disease; Adolescent; Adult; Blood Loss, Surgical; Case-Control Studies; Child; Cytokines; Female; Humans; Interleukin-6; Interleukin-8; Male; Malondialdehyde; Pancreatitis; Pilot Projects; Postoperative Complications; Prospective Studies; Risk Factors; Spinal Fusion; Tumor Necrosis Factor-alpha

The detection of graft rejection by bronchoalveolar lavage remains controversial.. To assess the value of bronchoalveolar lavage fluid in acute and chronic rejection after lung transplantation we analyzed bronchoalveolar lavage fluid cellular differential characteristics, lymphocyte sub-types and interleukin-6 (IL-6) and interleukin-8 (IL-8) cytokine levels in patients with exclusively either acute rejection (n = 37) or bronchiolitis obliterans (BO; n = 48). Both groups were compared with a control group of lung transplantation patients without rejection or infection, matched for the time the lavage was performed after lung transplantation.. The bronchiolitis obliterans group showed marked neutrophilia, high IL-8 and higher CD4(+)CD25(+) and CD8(+)CD45(+) bronchoalveolar lavage fluid levels when compared with their stable controls. When using a cut-off point of >3% neutrophils in the lavage, the sensitivity for BO is 87.0%, the specificity 77.6%. The sensitivity of IL-8 for BO when using a cut-off point of >71.4 pg/ml is 74.5%, the specificity 83.3%. Bronchoalveolar lavage fluid in acute rejection was characterized by marked lymphocytosis, but showed no difference when compared with stable controls in any of the lymphocyte sub-types studied. When using a cut-off point of <==1% lymphocytes in the lavage, the sensitivity for acute rejection (AR) is 40.4%, the specificity 95.6%. The marked neutrophilia, high IL-8 cytokine level and more activated lymphocyte population in bronchiolitis obliterans may indicate ongoing local allograft rejection.. In the present study we were not able to show any difference in lymphocyte sub-types when comparing acute rejection and control subjects. Cellular and soluble parameters in bronchoalveolar lavage fluid appear useful for diagnosing bronchiolitis obliterans.

Topics: Acute Disease; Adult; Bronchiolitis Obliterans; Bronchoalveolar Lavage Fluid; Cell Count; Chronic Disease; Female; Flow Cytometry; Graft Rejection; Humans; Interleukin-6; Interleukin-8; Lung Transplantation; Lymphocyte Subsets; Male; Sensitivity and Specificity

s: To determine whether talc (TL) and silver nitrate (SN), two effective pleurodesis agents, induce a systemic inflammatory response in the acute phase of experimental pleurodesis in rabbits.. Samples of blood and pleural fluid were collected after 6, 24, and 48 h from rabbits injected intrapleurally with 3 mL saline solution, TL (400 mg/kg), or 0.5% SN, and were assayed for WBC count, percentage of neutrophils, and levels of lactate dehydrogenase (LDH), interleukin (IL)-8, and vascular endothelial growth factor (VEGF). The pleural liquid production was compared in the three different groups. A sample of blood collected from animals preinjection was used as the control.. At 6 h after pleural injection, the mean blood WBC count and percentage of neutrophils were significantly elevated in the TL group, whereas the mean LDH and IL-8 levels were significantly increased in the SN group. VEGF was undetectable in the preinjection serum and saline solution-injected animals, but was increased in the serum after the pleural injection of both TL and SN to a comparable degree. SN elicited a more intense acute pleural inflammation reaction than did TL, with higher WBC count and IL-8 levels found in the pleural fluid, mainly within the first 6 h. LDH and VEGF levels, and pleural liquid production were also higher for SN, and they increased with time.. In the acute phase of pleural injection, TL induced a transient increase in blood WBC count and percentage of neutrophils, while SN induced increases in blood LDH and IL-8 levels. Both TL and SN induced significant increases in blood VEGF levels. SN induced an earlier and more intense acute pleural inflammation than TL. Pleural liquid VEGF levels were higher after SN injection and increased, as did pleural liquid production. These findings suggest that the intrapleural injection of TL and SN produce a systemic inflammatory response that may have a role in the pathogenesis of fever and ARDS, which occur with pleurodesis.

Topics: Acute Disease; Animals; Disease Models, Animal; Inflammation; Inflammation Mediators; Injections, Intralesional; Interleukin-8; Leukocyte Count; Male; Pleural Effusion; Pleurodesis; Rabbits; Random Allocation; Reference Values; Sensitivity and Specificity; Silver Nitrate; Talc; Vascular Endothelial Growth Factor A

The brain tissue damage after stroke is mediated partly by inflammation induced by ischaemia-reperfusion injury where the complement system plays a pivotal role. In the present study we investigated systemic complement activation and its relation to C-reactive protein (CRP), a known complement activator, and other inflammatory mediators after acute ischaemic stroke. Sequential plasma samples from 11 acute stroke patients were obtained from the time of admittance to hospital and for a follow-up period of 12 months. Nine healthy gender- and age-matched subjects served as controls. The terminal SC5b-9 complement complex (TCC), CRP, soluble adhesion molecules (L-, E- and P- selectin, ICAM, VCAM) and cytokines [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-8] were analysed. All parameters were within normal values and similar to the controls the first hours after stroke. Terminal complement complex (TCC) increased significantly from 0.54 to 0.74 AU/ml at 72 h (P = 0.032), reached maximum at 7 days (0.90 AU/ml, P < 0.001), was still significantly increased at 12 days (0.70 AU/ml, P = 0.009) and thereafter normalized. CRP increased significantly from 1.02 to 2.11 mg/l at 24 h (P = 0.023), remained significantly increased for 1 week (2.53-2.94 mg/l, P = 0.012-0.017) and thereafter normalized. TCC and C-reactive protein (CRP) correlated significantly (r = 0.36, P < 0.001). The increase in TCC and CRP correlated to the size of infarction (r = 0.80 and P = 0.017 for TCC; r = 0.72 and P = 0.043 for CRP). No significant changes were seen for adhesion molecules and cytokines. In conclusion, transitory systemic complement activation takes place after stroke. The early rise in CRP and the following TCC increase suggest a possible role for CRP in complement activation, which may contribute to inflammation after stroke.

Topics: Acute Disease; Aged; Brain Ischemia; C-Reactive Protein; Cell Adhesion Molecules; Complement Activation; Complement Membrane Attack Complex; Complement System Proteins; Glycoproteins; Humans; Interleukin-1; Interleukin-8; Middle Aged; Selectins; Stroke; Tumor Necrosis Factor-alpha

The infiltration of leukocytes into the glomeruli is a major factor in inflammatory glomerular damage in acute poststreptococcal glomerulonephritis (APSGN). Chemokines participate in leukocyte infiltration. The aim of the present study was to investigate the role of monocyte chemoattractant protein-1 (CCL2/MCP-1) and interleukin-8 (CXL8/IL-8) in APSGN with special emphasis on their role in the clinical course of renal disease. Twenty-one children with APSGN were studied. Serum and urinary CCL2/MCP-1 and CXL8/IL-8 levels were measured by ELISA. The relationships between urinary chemokines and the degree of proteinuria were investigated. Serum and urinary CCL2/MCP-1 levels were significantly higher in the acute phase than in the resolution phase and in controls ( P<0.05). Urinary CCL2/MCP-1 levels in the control group were significantly lower than in both the acute and resolution phases ( P=0.01 and P =0.001, respectively). In the acute phase, urinary CCL2/MCP-1 correlated with the extent of proteinuria ( r=0.58, P =0.006) but not with serum CCL2/MCP-1 levels ( r=0.21, P =0.36). Urinary and serum CXL8/IL-8 levels were significantly elevated in the acute phase compared with the resolution phase and controls ( P<0.05). A consistent increase in urinary CCL2/MCP-1 was found in the acute phase of patients with APSGN, and this correlates with the degree of proteinuria. Our results emphasize the important role of locally produced chemokines in immune-mediated glomerular injury.

Topics: Acute Disease; Adolescent; Chemokine CCL2; Child; Child, Preschool; Female; Glomerulonephritis; Humans; Interleukin-8; Male; Streptococcal Infections

The aim of the present study was to determine whether the presence of an infectious focus or of fever alone can predict bloodstream infection and whether levels of C-reactive protein, procalcitonin, interleukin (IL)-6, IL-8, and soluble IL-2 receptor (sIL-2R) improve the diagnosis of community-acquired bloodstream infection. Markers of systemic inflammation were studied in 92 patients with community-acquired infection. On admission to hospital, 54 patients had an infectious focus, 25 had fever without an infectious focus, and 13 had neither. The presence of focus or fever predicted bloodstream infection (n=13 patients) with a sensitivity of 100% (95% confidence interval, 75-100), a specificity of 16% (95%CI, 9-26), a negative predictive value of 100% (95%CI, 75-100), and a positive predictive value of 16% (95%CI, 9-26). Positive predictive values of C-reactive protein, procalcitonin, IL-6, IL-8, and sIL-2R, all measured on admission, were also low (33-44%). Eight febrile patients in whom an infectious focus was found during a 3-day follow-up period had higher on-admission IL-6 (P=0.005) and sIL-2R (P=0.046) levels than did 17 febrile patients without an infectious focus. In conclusion, markers of systemic inflammation do not improve the diagnosis of community-acquired bloodstream infection; however, they may aid in identifying patients with fever due to occult infection.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Biomarkers; Blood-Borne Pathogens; C-Reactive Protein; Cohort Studies; Confidence Intervals; Critical Illness; Emergency Service, Hospital; Female; Finland; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Predictive Value of Tests; Prognosis; Receptors, Interleukin-2; Risk Assessment; ROC Curve; Sampling Studies; Sensitivity and Specificity; Shock, Septic; Survival Rate

Adherence of hematopoietic progenitor cells (HPCs) to stroma is an important regulatory step in megakaryocytic differentiation. However, the mechanisms through which megakaryocytic progenitors are inhibited by stroma are poorly understood. We examined the role of sulfated glycoconjugates, such as proteoglycans (PGs), on human bone marrow stroma (hBMS). To this end, PG structure was altered by desulfation or enzymatic cleavage. PGs participated in adhesion of human HPC, as desulfation resulted in about 50% decline in adhesion to hBMS. Heparan sulfate proteoglycans (HSPGs) were found to be responsible by showing about 25% decline in adhesion after pre-incubation of HPC with heparin and about 15% decline in adhesion after enzymatic removal of HSPGs from hBMS. Furthermore, PGs were involved in binding cytokines. Both desulfation and enzymatic removal of stromal HSPGs increased release of megakaryocytopoiesis-inhibiting cytokines, that is, interleukin-8 (IL-8, 1.9-fold increase) and macrophage inflammatory protein-1alpha (MIP-1alpha, 1.4-fold increase). The megakaryocytic output of HPC grown in conditioned medium of desulfated stroma was decreased to 50% of the megakaryocytic output in CM of sulfated stroma. From these studies, it can be concluded that PGs in bone marrow, in particular HSPGs, are involved in binding HPC and megakaryocytopoiesis-inhibiting cytokines. Bone marrow stromal PGs thus reduce differentiation of HPC toward megakaryocytes.

Topics: Acute Disease; Antigens, CD34; Blood Proteins; Bone Marrow; Cell Adhesion; Cell Differentiation; Cells, Cultured; Chemokine CCL3; Chemokine CCL4; Culture Media, Conditioned; Eosinophil Major Basic Protein; Hematopoietic Stem Cells; Heparitin Sulfate; Humans; Interleukin-8; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Macrophage Inflammatory Proteins; Megakaryocytes; Proteoglycans; Stromal Cells

In acute myeloid leukemia (AML), cell proliferation and differentiation are uncoupled, causing a maturation block. Induction of terminal differentiation is a potential therapeutic strategy. 1alpha, 25(OH)2 Vitamin D3 regulates differentiation and is immunomodulatory at concentrations causing severe hypercalcemia, thus limiting its use. We investigated 1alpha, 25(OH)2 Vitamin D3 and 5 of its more potent analogs with reduced calcium resorbing activity for differentiation of blast cells from AML (FAB M1) patients, compared to TPA. Blast phenotype, p-glycoprotein expression, cytokine production, and lineage specificity were examined. The Vitamin D3 analogs had no effect on cell viability and proliferation. They induced incomplete differentiation, with increase in AP, NSE and NBT positivity of cells, but no cell sticking and spreading as observed with TPA. The analogs were more effective than the parent compound. They also inhibited the production of IL-6 and IL-8. Vitamin D3 and its analogs can induce differentiation of primary cells from AML patients in vitro, but may need to be combined with other agents for terminal differentiation of blasts and effective therapy in vivo.

Topics: Acute Disease; Calcitriol; Cell Adhesion; Cell Differentiation; Cells, Cultured; Cytokines; Dose-Response Relationship, Drug; Granulocyte Precursor Cells; Humans; Interleukin-6; Interleukin-8; Leukemia, Myeloid, Acute; Structure-Activity Relationship

To investigate the ability of sera from children with active Henoch-Schonlein purpura (HSP) to enhance endothelial interleukin (IL) 8 production and intercellular adhesion molecule (ICAM)-1 expression.. Nine children with active HSP and nine normal healthy children were enrolled. IL8 serum levels of patients and controls at different stages were analysed. Production of IL8 and expression of ICAM-1 by human umbilical venous endothelial cells were detected (ELISA for IL8, flow cytometry for ICAM-1) and compared under various stimuli, including sera of patients at different stages, sera of controls, and medium alone.. Serum levels of IL8 were increased at the acute stage. Levels of IL8 in supernatants from human umbilical venous endothelial cells (HUVEC) co-cultured with sera from children with active HSP were significantly higher than those from HUVEC without any treatment (p = 0.001), HUVEC treated with inactive sera (p = 0.004), and HUVEC treated with sera from healthy controls (p = 0.004). Sera from patients and from controls did not enhance the expression of ICAM-1 on HUVEC.. Some factors may be present in sera from children with active HSP that could activate endothelial cells to produce IL8. This process may account, in part, for the mechanisms of perivascular neutrophil infiltration and leucocytosis in HSP.

Topics: Acute Disease; Case-Control Studies; Cells, Cultured; Child; Endothelial Cells; Female; Humans; IgA Vasculitis; Immune Sera; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Umbilical Veins

Alterations of the immune system may have a role in thrombogenesis. Artery sites occluded with thrombi apparently release pro-inflammatory cytokines. Non-arteritic anterior ischaemic optic neuropathy (NAION) results from occlusion of the blood supply to the optic nerve. The aim of this study was to analyse levels of pro-inflammatory cytokines in patients with acute event of NAION.. Study participants included 10 patients (12 eyes) with NAION and 20 age matched controls with the same risk factors for atherosclerosis disease. Peripheral blood samples were obtained immediately at the acute onset of NAION. Plasma interleukin 8 (IL-8), IL-6, and tumour necrosis factor alpha (TNF-alpha) levels were measured immediately following diagnosis and during the follow up intervals.. The plasma levels of IL-8 were significantly higher in NAION patients at the time of diagnosis in comparison to the control group (p = 0.002), and decreased during the follow up period (6-12 months) (p = 0.05). There were no differences in plasma levels of IL-6 and TNF-alpha between NAION patients and controls, either in the acute phase or during the follow up period.. Plasma levels of IL-8 are elevated during the acute phase of NAION, but not IL-6 and TNF-alpha. These elevated levels are in accordance with other acute vascular thrombosis. The clinical significance of these findings should be further evaluated.

Topics: Acute Disease; Aged; Aged, 80 and over; Anterior Eye Segment; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Optic Neuropathy, Ischemic; Tumor Necrosis Factor-alpha

To evaluate the kinin system components and selected cytokines in plasma and cerebrospinal fluid (CSF) of patients with neuropsychiatric lupus (NPL).. We studied 29 women with active NPL and 29 healthy women matched to patients for age. Low (LKg) and high molecular weight kininogen (HKg) and cytokine concentrations [interleukin 1beta (IL-1beta), IL-6, IL-8, IL-10, and tumor necrosis factor-a (TNF-a)] were determined by ELISA. The activities of tissue kallikrein, plasma prekallikrein, and kininase II were assayed by their action on selective substrates.. Compared to controls, patients with NPL presented increased plasma and CSF levels of LKg, HKg, and prekallikrein, increased activity of tissue kallikrein and kininase II, and increased levels of IL-6, IL-10, and TNF-a (p < 0.001 each comparison). IL-1beta levels were increased in patient plasma (p < 0.001), whereas plasma IL-8 levels did not differ from controls. IL-1beta and IL-8 were not detected in CSF of patients or controls.. The increased levels of kininogen fractions, kallikreins, and kininase II in patient plasma and CSF indicate overactivity of the kinin system, suggesting intense kinin production. Since kinins may induce the production of proinflammatory cytokines including IL-1beta, IL-6, and TNF-a, these findings support the participation of kinins and cytokines in the acute manifestations of NPL. Most of the variables evaluated in patients' CSF increased proportionally in relation to plasma levels. In contrast, the activity of tissue kallikrein in patient CSF increased out of proportion to plasma levels, appearing to be locally synthesized in response to brain involvement.

Topics: Acute Disease; Adult; Cytokines; Female; Humans; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Kininogen, High-Molecular-Weight; Kininogen, Low-Molecular-Weight; Lupus Vasculitis, Central Nervous System; Middle Aged; Peptidyl-Dipeptidase A; Prekallikrein; Tissue Kallikreins; Tumor Necrosis Factor-alpha

Macrophage migration inhibitory factor (MIF), originally described as an inhibitor of the random migration of macrophages, has been shown recently to be involved in the pathogenesis of several inflammatory diseases such as sepsis. The aim of this study was to clarify the role of MIF in acute pancreatitis (AP).. Hemorrhagic necrotizing pancreatitis and edematous pancreatitis were induced by the injection of taurocholic acid (TCA pancreatitis) and cerulein (cerulein pancreatitis), respectively, on male Wistar rats. MIF levels in ascitic fluids, serum, and the organs were determined. The effects of anti-MIF antibody were examined on the prognosis of rats with TCA pancreatitis and of female CD-1 mice with choline-deficient, ethionine-supplemented, diet-induced model of severe AP. In addition, serum MIF levels in AP patients and in healthy controls were measured.. Serum and ascitic MIF levels in TCA pancreatitis were increased rapidly and decreased gradually thereafter. Ascitic MIF levels were also increased in cerulein pancreatitis, but to a lesser degree. MIF level was increased in the lung in TCA pancreatitis, but not in the pancreas and the liver. Prophylactic (1 hour before and immediately after induction) administration of anti-MIF antibody significantly improved the survival rate of rats with TCA pancreatitis. The survival rate of mice with severe AP was also improved significantly by the antibody treatment. Serum MIF levels were higher in severe AP patients than mild AP patients and healthy controls.. These results suggest a role of MIF in the pathogenesis of severe AP.

Topics: Acute Disease; Animals; Antibodies; Ascitic Fluid; Cholagogues and Choleretics; Choline; Ethionine; Female; Humans; Interleukin-8; Lung; Macrophage Migration-Inhibitory Factors; Macrophages, Peritoneal; Male; Mice; Mice, Inbred Strains; Pancreatitis; Rats; Rats, Wistar; Severity of Illness Index; Survival Analysis; Taurocholic Acid

To understand the dynamics of the intraarticular acute inflammatory phase of an anterior cruciate ligament (ACL) injured knee, we analyzed the level of inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8, IL-1ra, and IL-10) in joint fluid samples aspirated from 34 knees following an acute ACL injury. The samples were divided into the following five groups according to the duration from injury to aspiration: within 24 h (n=5), 2-3 days (n=14), 4-6 days (n=5), 7-9 days (n=5), 10-14 days (n=4), and 15-21 days (n=3). For comparison, 7 samples were also aspirated from 4 patients with osteoarthritis and 3 with postmenisectomy hydrops (chronic arthritis group). The highest levels of inflammatory cytokines were detected in the ACL-injury group within 24 h of the injury, and the levels decreased thereafter. While there were several patterns of decrease, nearly all of the inflammatory cytokines decreased to the level of that in the chronic arthritis group within 1 week. These dynamics are similar to those reported for inflammatory cytokines in wound fluid during wound healing, and suggest that the intraarticular healing process also progresses in ACL injured knees.

Topics: Acute Disease; Adolescent; Adult; Anterior Cruciate Ligament Injuries; Arthroscopy; Cohort Studies; Cytokines; Female; Humans; Inflammation Mediators; Injury Severity Score; Interleukin-10; Interleukin-6; Interleukin-8; Knee Injuries; Male; Middle Aged; Predictive Value of Tests; Probability; Prognosis; Prospective Studies; Radioimmunoassay; Synovial Fluid; Time Factors; Tumor Necrosis Factor-alpha; Wound Healing

Topics: Acute Disease; Humans; Inflammation; Interleukin-8; Pancreatitis; Phospholipases A; Pyridines

Lung tissue removed from neonatal calves with acute Mannheimia haemolytica pneumonia showed that rapid up-regulation of the basal mRNA expression of tracheal antimicrobial peptide (TAP), NF-kappa B, and intercellular adhesion molecule 1 occurred after infection; TAP and interleukin 8 expression were highly correlated. This work suggests that the coordinated expression of beta-defensin and inflammatory elements occurs during bacterial pneumonia.

Topics: Active Transport, Cell Nucleus; Acute Disease; Animals; Animals, Newborn; Antimicrobial Cationic Peptides; Cattle; Intercellular Adhesion Molecule-1; Interleukin-8; Lung; NF-kappa B; Pneumonia, Bacterial; RNA, Messenger

Chemokines and T-lymphocytes play an important role in lower respiratory tract inflammation. This study evaluated the concentration of IL-8 and count of T-lymphocytes expressing adhesion molecules LFA-1, Mac-1, Lsel and their correlation in patients with asthma and COPD in periods of exacerbation and clinical improvement (after seven days of anti-inflammatory treatment). In all subjects bronchoscopic examination with BAL procedure were done in exacerbation period and after seven days of treatment. The concentration of IL-8 was measured by ELISA, and the expression of adhesion molecules by biotin-streptavidin methods. The highest concentration of IL-8 was observed in asthma patients in clinical improvement period, and the highest count of T-lymphocytes was observed in patients with COPD in remission phase. Increased concentration of chemokines could have been influenced by type of treatment administered, especially beta 2-mimetics. The significant correlation observed in COPD patients between IL-8 concentration and counts of T-cells expressing LFA-1 (r = 0.44), Mac-1 (r = 0.49), Lsel (r = 0.42) in exacerbation period suggest a chemotactic influence of IL-8 on T-lymphocytes.

Topics: Acute Disease; Adult; Asthma; Bronchoalveolar Lavage Fluid; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; L-Selectin; Lymphocyte Function-Associated Antigen-1; Macrophage-1 Antigen; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; T-Lymphocytes; Time Factors

Endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis provides a model to study the time course of cytokine release during the initiation phase of pancreatitis. The early changes of inflammatory cytokines after ERCP have been unclear.. To evaluate the early changes in serum levels of proinflammatory and antiinflammatory cytokines after ERCP and to assess their value in the early recognition of post-ERCP pancreatitis.. Seventy-eight consecutive patients undergoing ERCP were prospectively studied. The serum concentrations of tumor necrosis factor alpha, interleukin-1beta, interleukin-6, interleukin-8, and interleukin-10 were determined immediately prior to and 1, 4, 8, and 24 hours after ERCP.. Seven of 78 patients (9.0%) developed post-ERCP pancreatitis. Serum levels of tumor necrosis factor alpha, interleukin-1beta, interleukin-6, interleukin-8, and interleukin-10 significantly increased at 8 and 24 hours but not at 1 and 4 hours after ERCP in patients with post-ERCP pancreatitis, in comparison with patients without pancreatitis. Using a cutoff level of 36 pg/mL for interleukin-6 at 8 hours after ERCP, we found that the sensitivity and specificity for recognition of post-ERCP pancreatitis were 100% and 87%, respectively. Serum levels of interleukin-6 and interleukin-8 modestly increased from baseline values, 1 to 24 hours after uncomplicated ERCP.. Proinflammatory and antiinflammatory cytokines significantly increased in the early stage after ERCP-induced pancreatitis. Among the inflammatory cytokines, interleukin-6 is the most useful for recognition of post-ERCP pancreatitis.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Cholangiopancreatography, Endoscopic Retrograde; Cytokines; Female; Humans; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Pancreatitis; Time Factors; Tumor Necrosis Factor-alpha

We have applied immunohistology and in situ hybridization to bronchial biopsies of patients with chronic obstructive pulmonary disease (COPD) to examine neutrophil recruitment and to determine neutrophil chemoattractant and CXC receptor (CXCR) 1 and CXCR2 gene expression associated with acute severe exacerbations. Cells were counted in endobronchial biopsies of (1) patients with COPD intubated for exacerbations (E-COPD; n = 15), (2) those with COPD in a stable phase of their disease (S-COPD; n = 7), and (3) nonsmoker surgical control subjects intubated for a nonrespiratory surgical procedure (n = 15). In comparison with the nonrespiratory surgical procedure and S-COPD groups, neutrophilia and gene expression for epithelial-derived neutrophil attractant-78 (CXCL5), interleukin-8 (CXCL8), CXCR1, and CXCR2 were each upregulated in the E-COPD group (p < 0.01); compared with the S-COPD group, by 97-, 6-, 6-, 3-, and 7-fold, respectively (p < 0.01). In E-COPD, there was a significant positive association between the number of neutrophils and CXCR2 mRNA-positive cells (r = 0.79; p < 0.01) but not between the number of neutrophils and CXCR1 mRNA-positive cells. At the time of sampling of the mucosa, there was no association between neutrophil number and either the length of intubation or viral infection. Thus, in COPD, in addition to CXCL8 and CXCR1, CXCL5 and CXCR2 appear to play important roles in the airway neutrophilia characteristic of severe exacerbations.

Topics: Acute Disease; Aged; Biopsy; Bronchoscopy; Case-Control Studies; Chemokine CXCL5; Chemokines, CXC; Female; Forced Expiratory Volume; Gene Expression; Humans; Immunohistochemistry; In Situ Hybridization; Inflammation; Interleukin-8; Male; Middle Aged; Neutrophil Infiltration; Pulmonary Disease, Chronic Obstructive; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Respiratory Mucosa; Severity of Illness Index; Up-Regulation

Chronic obstructive pulmonary disease (COPD) is often associated with peripheral muscle weakness, which is caused by several factors. Acute exacerbations may contribute, but their impact on muscle force remains unclear. Correlations between peripheral muscle force and inflammatory and anabolic markers have never been studied in COPD. The effect of an acute exacerbation on quadriceps peak torque (QPT) was therefore studied in hospitalised patients, and the aforementioned correlations were examined in hospitalised and in stable patients.. Lung function, respiratory and peripheral muscle force, and inflammatory and anabolic markers were assessed in hospitalised patients on days 3 and 8 of the hospital admission and 90 days later. The results on day 3 (n=34) were compared with those in clinically stable outpatients (n=13) and sedentary healthy elderly subjects (n=10).. Hospitalised patients had lowest mean (SD) QPT (66 (22)% predicted) and highest median (IQR) levels of systemic interleukin-8 (CXCL8, 6.1 (4.5 to 8.3) pg/ml). Insulin-like growth factor I (IGF-I) tended to be higher in healthy elderly subjects (p=0.09). QPT declined between days 3 and 8 in hospital (mean -5% predicted (95% CI -22 to 8)) and partially recovered 90 days after admission to hospital (mean 6% predicted (95% CI -1 to 23)). QPT was negatively correlated with CXCL8 and positively correlated with IGF-I and lung transfer factor in hospitalised and in stable patients.. Peripheral muscle weakness is enhanced during an acute exacerbation of COPD. CXCL8 and IGF-I may be involved in the development of peripheral muscle weakness in hospitalised and in stable patients with COPD.

Topics: Acute Disease; Aged; Cross-Sectional Studies; Forced Expiratory Volume; Hospitalization; Humans; Insulin-Like Growth Factor I; Interleukin-8; Muscle Weakness; Pulmonary Disease, Chronic Obstructive; Vital Capacity

Severe acute pancreatitis is associated with a high mortality, especially when compared with mild acute pancreatitis. Early intervention in patients with severe acute pancreatitis has been shown to improve mortality. The value of cytokines (interleukin [IL]-6, IL-8 and tumor necrosis factor [TNF]-alpha) in diagnosing severe acute pancreatitis at an early stage was studied.. Thirty-six patients with acute pancreatitis were prospectively evaluated. Age-matched controls were obtained from healthy volunteers. Levels of IL-6, IL-8, and TNF-alpha were obtained within 24 hours of admission. Ranson's prognostic signs and Bank's clinical criteria were used to differentiate patients into mild and severe pancreatitis.. There was significant difference in IL-6 levels between controls and mild pancreatitis, controls and severe pancreatitis, and mild and severe pancreatitis. IL-8 levels were significantly different between controls and severe pancreatitis and mild and severe pancreatitis. There was no significant difference between controls and mild pancreatitis. The results for TNF-alpha were similar to the findings for IL-8.. IL-6, IL-8, and TNF can be used independently in differentiating mild acute pancreatitis from early severe acute pancreatitis.

Topics: Acute Disease; Adult; Case-Control Studies; Diagnosis, Differential; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Pancreatitis; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Severity of Illness Index; Time Factors; Tumor Necrosis Factor-alpha

Although cigarette smoking is a recognized cause of acute eosinophilic pneumonia (AEP), and an increase in eosinophils in the lung is a common occurrence in AEP, early-phase neutrophilia in AEP is not well understood. We describe three cases of cigarette smoke (menthol type)-induced AEP with neutrophilia in the lungs or blood. Increased in-vitro production of the neutrophil chemoattractant interleukin (IL)-8 by human bronchial epithelial cells (HBECs) was correlated with neutrophilia. We suggest that IL-8 released from HBECs is involved in neutrophilia in the lung in AEP, and is newly recognized as an important factor in the early phase of AEP development.

Topics: Acute Disease; Adolescent; Adult; Biopsy; Bronchi; Cell Culture Techniques; Female; Humans; Interleukin-8; Leukocytosis; Lung; Male; Neutrophils; Nicotiana; Pulmonary Eosinophilia; Respiratory Mucosa; Smoke; Smoking

Plasma pancreatic-type Poly-C specific ribonuclease (P-RNase)-enzyme activity increases in patients with acute pancreatitis (AP) who develop pancreatic necrosis and severe disease course. It is considered as a marker of pancreatic tissue destruction. The aim of this study was to estimate interrelations between major inflammatory cytokines such as: interleukin 6 (IL-6), interleukin 8 (IL-8) and tumor necrosis factor soluble receptors: sTNFR55 and sTNFR75 output, and plasma P-RNase activity. The study was carried out in a group of 56 patients with AP, where 20 developed pancreatic necrosis. It was found that serum P-RNase concentration and levels of all studied inflammatory cytokines significantly increase already in the first day from diagnose of the disease (2.5 folds for P-RNase, 20 for IL-8, about 200 for IL-6 and 1.5 for receptors, respectively). In the first day from admission to hospital, P-RNase activity significantly correlated with plasma concentration of studied inflammatory cytokines. The most pronounced correlation was found for P-RNase and IL-6 in days 1-4 from diagnose, manifested by Pearson correlation r coefficients amounting to 0.86, 0.79, 0.60 and 0.57 respectively (p<0.001). Dividing the studied AP patients into two groups, varying in severity of disease a significant differences in P-RNase and IL-6, IL-8 and sTNFR55/sTNFR75 were found. In patients with acute necrotizing pancreatitis P-RNase significantly correlate with levels of major inflammatory cytokines. Carried out studies suggest that activity of P-RNase reflects severity of inflammatory reaction, which is dependent on development of pancreatic injury and tissue necrosis in AP.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Amylases; Antigens, CD; Endoribonucleases; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Pancreatitis; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type II; Ribonuclease, Pancreatic; Severity of Illness Index; Solubility; Time Factors; Tumor Necrosis Factor-alpha

Sixteen patients with acute middle cerebral artery stroke were studied to correlate neuroinflammatory markers with perfusion- and diffusion-weighted magnetic resonance imaging (MRI) lesion volumes (PWI and DWI). At arrival (less than 6 hours), plasmatic matrix metalloproteinase (MMP)-9, MMP-2, interleukin (IL)-6, IL-8, intercellular adhesion molecule (ICAM)-1, and tumor necrosis factor (TNF)-alpha were serially measured (by ELISA), and MRI was performed. In cerebral ischemia, tissue destruction seems related to matrix metalloproteinases expression because baseline MMP-9 was the only predictor of the infarct volume measured as a DWI lesion (lineal regression: b = 0.50, 0.25-0.74; P < 0.001). Moreover, the extent of hypoperfused brain area (PWI) was associated with a proinflammatory cytokine release in the next hours (TNF-alpha and IL-6).

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Diffusion Magnetic Resonance Imaging; Female; Humans; Infarction, Middle Cerebral Artery; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Predictive Value of Tests; Prospective Studies; Tumor Necrosis Factor-alpha

Neutrophil infiltration of the lung is characteristic of early posttraumatic acute respiratory distress syndrome (ARDS). This study examines the ability of neutrophils isolated (over the first 24 hrs) from the peripheral blood of patients admitted after major trauma to migrate in response to interleukin-8. Interleukin-8 is elevated in the lung within 2 hrs of major trauma in patients who later develop ARDS, and thus it plays a central role in the recruitment of neutrophils to the lung and their subsequent activation. We hypothesized that enhanced interleukin-8-mediated neutrophil migratory activity in the early postinjury phase, before the development of ARDS, may be a crucial factor in the etiology of ARDS.. Prospective observational study.. University Hospital Wales, the Royal Gwent Hospital, and East Glamorgan General Hospital. Laboratory work was conducted at the Institute of Nephrology.. Adult blunt trauma victims with Injury Severity Score > or = 18.. Neutrophils were isolated from citrated blood from 17 adult blunt major trauma patients at admission (0 hrs) and 8 and 24 hrs later. Identical samples were obtained from normal laboratory volunteers (n = 9). The neutrophil count in each specimen was measured, and the number of neutrophils migrating across porous tissue culture inserts in response to defined concentrations of interleukin-8 (0, 10, 30, and 100 ng/mL) was quantitated by peroxidase assay. Neutrophil counts in the whole blood specimens obtained from those later developing ARDS were elevated significantly at admission and declined rapidly throughout the next 24 hrs. Significantly greater numbers of trauma patients' neutrophils migrated to concentrations of interleukin-8 (30 and 100 ng/mL) at each time point when compared with normal volunteers (Mann-Whitney U test, p <.05). Neutrophils isolated from major trauma patients exhibited an enhanced migratory response to high concentrations of interleukin-8 throughout the first 24 hrs of admission, in contrast to the normal physiologic attenuation of migration seen in neutrophils isolated from normal laboratory volunteers.. These data indicate that major blunt trauma enhances the migratory capacity of circulating neutrophils. This is manifest within 2 hrs of admission and may be attributable to alteration in interleukin-8 receptor expression, affinity, or downstream signaling. In patients who later develop ARDS, initially elevated circulating neutrophil counts decrease rapidly, over the same time course. Early enhanced neutrophil migratory activity coupled with elevated pulmonary concentrations of interleukin-8 may be central to the establishment of the neutrophil infiltration that is characteristic of ARDS.

Topics: Acute Disease; Adult; Cell Movement; Humans; Interleukin-8; Leukocyte Count; Neutrophil Infiltration; Neutrophils; Prospective Studies; Respiratory Distress Syndrome; Risk Factors; Time Factors; Trauma Severity Indices; Wales; Wounds, Nonpenetrating

Topics: Acute Disease; Chemokine CXCL1; Chemokine CXCL5; Chemokines; Chemokines, CXC; Chemotactic Factors; Growth Substances; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Pancreatitis

Cytokines regulate cellular immune activity and are produced by a variety of cells, especially lymphocytes, monocytes, and macrophages. Multiparameter flow cytometry is often used to examine cell-specific cytokine production after in vitro phorbol 12-myristate 13-acetate and ionomycin induction, with brefeldin A or other agents added to inhibit protein secretion. Spontaneous ex vivo production reportedly rarely occurs. We examined the spontaneous production of interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) by peripheral-blood B lymphocytes, T cells, CD8(-) T cells, CD8(+) T cells, CD3(-) CD16/56(+) lymphocytes (natural killer [NK] cells), CD3(+) CD16/56(+) lymphocytes (natural T [NT] cells), and/or monocytes of 316 acutely ill hospitalized persons and 62 healthy adults in Malawi, Africa. We also evaluated the relationship between spontaneous and induced cytokine production. In patients, spontaneous TNF-alpha production occurred most frequently, followed in descending order by IFN-gamma, IL-8, IL-4, IL-10, IL-6, and IL-2. Various cells of 60 patients spontaneously produced TNF-alpha; for 12 of these patients, TNF-alpha was the only cytokine produced spontaneously. Spontaneous cytokine production was most frequent in the immunoregulatory cells, NK and NT. For IL-2, IL-4, IL-6, IL-8, and IL-10, spontaneous cytokine production was associated with greater induced production. For TNF-alpha and IFN-gamma, the relationships varied by cell type. For healthy adults, IL-6 was the cytokine most often produced spontaneously. Spontaneous cytokine production was not unusual in these acutely ill and healthy persons living in an area where human immunodeficiency virus, mycobacterial, malaria, and assorted parasitic infections are endemic. In such populations, spontaneous, as well as induced, cell-specific cytokine production should be measured and evaluated in relation to various disease states.

Topics: Acute Disease; Adolescent; Adult; Child; Cytokines; Flow Cytometry; Humans; Immunity, Cellular; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Lymphocytes; Monocytes; Tumor Necrosis Factor-alpha

The aim of this study was to clarify the correlation between cytokine profile in colonic mucosa with disease activity and response to granulocytapheresis (GCAP) in patients with ulcerative colitis (UC), using a reliable, reproducible quantitative method.. Colonoscopic biopsies of inflamed colonic mucosa (16 patients, 21 cases) and uninflamed colonic mucosa (25 patients, 33 cases) were obtained from UC patients. Messenger (m)RNA was extracted and subjected to realtime polymerase chain reaction for quantitative measurement of interleukin (IL)-12, interferon-gamma, tumor necrosis factor-alpha, IL-4, IL-8, and IL-18 mRNAs. In seven patients with high disease activity despite prednisolone (PSL) treatment (> or = 20 mg/day), one course of GCAP was conducted, and pre- and post-GCAP cytokine profiles were determined.. In inflamed colonic mucosa of UC patients, three cytokine profiles were observed: 1) high expression of interferon-gamma, tumor necrosis factor-alpha, and IL-4 mRNAs but low expression of IL-8 mRNA; 2) high expression of IL-8 mRNA and low expression of others; and 3) low expression of all cytokines examined. Inflamed colonic mucosa of patients with high disease activity showed the second pattern. Inflamed colonic mucosa of patients who were not treated with PSL and who had low disease activity showed the first pattern, whereas those on high-dose PSL exhibited the second pattern. IL-8 mRNA was significantly higher in inflamed UC samples than in uninflamed samples. GCAP was effective in five of seven PSL-resistant patients (71.4%). IL-8 was the only cytokine that correlated with effectiveness of GCAP. Compared with GCAP nonresponders, responders had significantly higher IL-8 mRNA before GCAP and showed marked reduction of IL-8 mRNA after GCAP.. IL-8 mRNA was significantly increased in inflamed mucosa of UC. Patients with high IL-8 mRNA expression in colonic mucosa despite PSL treatment were responsive to GCAP. Therefore, quantitative measurement of mucosal IL-8 mRNA may be useful in predicting the response to GCAP.

Topics: Acute Disease; Adult; Aged; Chronic Disease; Colitis, Ulcerative; Colon; Cytokines; DNA, Complementary; Female; Granulocytes; Humans; Inflammation; Interferon-gamma; Interleukin-4; Interleukin-8; Intestinal Mucosa; Leukapheresis; Male; Middle Aged; Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha

Much evidence implicates IL-8 as a major mediator of inflammation and joint destruction in rheumatoid arthritis. The effects of IL-8 and its related ligands are mediated via two receptors, CXCR1 and CXCR2. In the present study, we demonstrate that a potent and selective nonpeptide antagonist of human CXCR2 potently inhibits (125)I-labeled human IL-8 binding to, and human IL-8-induced calcium mobilization mediated by, rabbit CXCR2 (IC(50) = 40.5 and 7.7 nM, respectively), but not rabbit CXCR1 (IC(50) = >1000 and 2200 nM, respectively). These data suggest that the rabbit is an appropriate species in which to examine the anti-inflammatory effects of a human CXCR2-selective antagonist. In two acute models of arthritis in the rabbit induced by knee joint injection of human IL-8 or LPS, and a chronic Ag (OVA)-induced arthritis model, administration of the antagonist at 25 mg/kg by mouth twice a day significantly reduced synovial fluid neutrophils, monocytes, and lymphocytes. In addition, in the more robust LPS- and OVA-induced arthritis models, which were characterized by increased levels of proinflammatory mediators in the synovial fluid, TNF-alpha, IL-8, PGE(2), leukotriene B(4), and leukotriene C(4) levels were significantly reduced, as was erythrocyte sedimentation rate, possibly as a result of the observed decreases in serum TNF-alpha and IL-8 levels. In vitro, the antagonist potently inhibited human IL-8-induced chemotaxis of rabbit neutrophils (IC(50) = 0.75 nM), suggesting that inhibition of leukocyte migration into the knee joint is a likely mechanism by which the CXCR2 antagonist modulates disease.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Chemotaxis, Leukocyte; Chronic Disease; Female; Humans; In Vitro Techniques; Interleukin-8; Lipopolysaccharides; Neutrophils; Ovalbumin; Rabbits; Receptors, Interleukin-8B; Recombinant Proteins; Urea

Cytokines and leukocyte adhesion molecules are activated and found in increased concentrations in bacterial infection. The purpose of this study was to investigate whether some of these new serum markers could be feasible as a single on-admission test to predict acute appendicitis (AA).. In an open prospective study the diagnostic potentials of two cytokine measurements (interleukin-6 and interleukin-8), soluble leukocyte adhesion molecule (CD44), C-reactive protein (CRP) and white blood cell (WBC) count were compared in 80 consecutive patients who had undergone surgery for suspected AA. The diagnostic performance of each parameter was tested by using receiver operating characteristic (ROC) curves.. Phlegmonous AA was found in 34%, gangrenous AA in 40% and perforated AA in 5% of the patients. The proportion of negative explorations was 21%. Preoperative serum concentrations of IL-6 and CRP were elevated only in gangrenous and perforated AA. The concentrations of IL-8 and CD44 remained unchanged in AA. The sensitivity (84%), specificity (79%) and diagnostic accuracy (82%) of IL-6 were higher than the values for CRP, WBC, IL-8 and CD44 in predicting AA.. ROC analysis confirmed that IL-6 showed the best trend in the diagnosis of AA. However, the diagnosis of AA was not greatly improved by any of the new serum markers as single on-admission tests.

Topics: Acute Disease; Adult; Appendicitis; Biomarkers; C-Reactive Protein; Child; Female; Humans; Hyaluronan Receptors; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity

The effect of inhaled nitric oxide (NO) on inflammatory process in acute lung injury (ALI) is unclear. The aims of this study were to 1) examine whether inhaled NO affects the biochemical lung injury parameters and cellular inflammatory responses and 2) determine the effect of inhaled NO on the activation of nuclear factor-kappa B (NF-kappa B) in lipopolysaccharide (LPS)-induced ALI. Compared with saline controls, rabbits treated intravenously with LPS showed increases in total protein and lactate dehydrogenase in the bronchoalveolar lavage (BAL) fluid, indicating ALI. LPS-treated animals with NO inhalation (LPS-NO) showed significant decreases in these parameters. Neutrophil numbers in the BAL fluid, the activity of reactive oxygen species in BAL cells, and the levels of interleukin (IL)-1 beta and IL-8 in alveolar macrophages were increased in LPS-treated animals. In contrast, neutrophil numbers and these cellular activities were substantially decreased in LPS-NO animals, compared with LPS-treated animals. NF-kappa B activation in alveolar macrophages from LPS-treated animals was also markedly increased, whereas this activity was effectively blocked in LPS-NO animals. These results suggest that inhaled NO attenuates LPS-induced ALI and pulmonary inflammation. This attenuation may be associated with the inhibition of NF-kappa B activation.

Topics: Acute Disease; Administration, Inhalation; Animals; Bronchoalveolar Lavage Fluid; Cell Movement; Interleukin-1; Interleukin-8; L-Lactate Dehydrogenase; Lipopolysaccharides; Macrophages, Alveolar; Neutrophils; NF-kappa B; Nitric Oxide; Pneumonia; Proteins; Rabbits; Reactive Oxygen Species

Hyperglycaemia, in insulin-dependent or independent diabetes mellitus, promotes endothelial cell (EC) dysfunction and is a major factor in the development of macro- or microvascular diseases. The mechanisms and the disease-related genes in vascular diseases resulting from hyperglycaemia are poorly understood. Macroarrays. bearing a total of 588 cDNA known genes, were used to analyze HUVEC gene transcription subjected to 25 or 5-mM glucose for 24 h. Isolated mRNA derived from treated first passage HUVEC were reverse transcribed, 32P labeled, and hybridized to the cDNA macroarrays. Results show that acute hyperglycaemia induces an up-regulation of seven major genes, four of which were not previously reported in the literature. Northern blot analyses, performed on these 4 genes, confirm macroarrays results for alphav, beta4, c-myc, and MUC18. Moreover, time course analysis (0, 2, 4, 8, 2, 16, 24 h) of alphav, beta4 c-myc, and MUC18 mRNA expression, observed by northern blot assays, showed a peak at time points situated between 2 to 8 h. The 3 other genes (ICAM-1, beta1, and IL-8), were shown by others to be significantly upregulated after glucose stimulation. Furthermore, ELISA assays performed on the supernatant of HUVEC culture medium showed a significant increase of IL-8 for cells treated with 25-mM compared to 5-mM glucose. Identified genes, upregulated in endothelial cells as a result of acute hyperglycaemia, may serve as therapeutic or diagnostic targets in vascular lesions present in diabetic patients. These results also demonstrate the use of cDNA macroarrays as an effective approach in identifying genes implicated in a diseased cell.

Topics: Acute Disease; Antigens, CD; Antigens, Surface; CD146 Antigen; Cells, Cultured; Chemokine CCL2; DNA, Complementary; Endothelium, Vascular; Gene Expression Regulation; Genes, myc; Glucose; Humans; Hyperglycemia; Integrin alphaV; Integrin beta1; Integrin beta4; Intercellular Adhesion Molecule-1; Interleukin-8; Membrane Glycoproteins; Neural Cell Adhesion Molecules; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins c-myc; RNA, Messenger

The formation of alpha(2)-macroglobulin (alpha(2)-M)/interleukin-8 (IL-8) complexes may influence the biological activity of IL-8 and the quantitative assessment of IL-8 activity. Therefore, in this study, concentrations of free IL-8 and IL-8 complexes with alpha(2)-M were measured in pulmonary edema fluid samples from patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and compared with control patients with hydrostatic pulmonary edema. Patients with ALI/ARDS had significantly higher concentrations of alpha(2)-M (P < 0.01) as well as alpha(2)-M/IL-8 complexes (P < 0.05). Because a substantial amount of IL-8 is complexed to alpha(2)-M, standard assays of free IL-8 may significantly underestimate the concentration of biologically active IL-8 in the distal air spaces of patients with ALI/ARDS. Furthermore, IL-8 bound to alpha(2)-M retained its biological activity, and this fraction of IL-8 was protected from proteolytic degradation. Thus complex formation may modulate the acute inflammatory process in the lung.

Topics: Acute Disease; alpha-Macroglobulins; Extravascular Lung Water; Humans; In Vitro Techniques; Interleukin-8; Macrophages, Alveolar; Neutrophils; Pancreatic Elastase; Pulmonary Edema; Respiratory Distress Syndrome

Multiple organ dysfunction syndrome secondary to systemic leucocyte activation is the major cause of death following an attack of acute pancreatitis. Although plasma levels of interleukin (IL) 8 are known to be raised in acute pancreatitis, levels of other CXC chemokines such as growth-related oncogene (GRO) alpha and epithelial neutrophil-activating protein (ENA) 78, which are also potent neutrophil chemoattractants and activators, have not been measured.. Timed plasma samples were obtained from 51 patients with acute pancreatitis, 27 with a severe attack and 24 with mild disease according to the Atlanta classification. Samples were analysed to determine levels of C-reactive protein (CRP), IL-8, GRO-alpha and ENA-78.. Plasma levels of IL-8, GRO-alpha and ENA-78 were increased in patients with severe as opposed to mild acute pancreatitis as early as 24 h following disease onset. Using cut-off levels of 7 pg/ml for IL-8, 70 pg/ml for GRO-alpha and 930 pg/ml for ENA-78, peak levels within the first 24 h of admission had an accuracy of 81, 71 and 87 per cent respectively in predicting the severity of an attack of acute pancreatitis.. In patients with severe acute pancreatitis plasma levels of GRO-alpha and ENA-78 were raised in addition to those of IL-8, suggesting that all three chemokines are involved in the inflammatory response in this condition.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; C-Reactive Protein; Chemokine CXCL5; Chemokines; Chemokines, CXC; Female; Growth Substances; Humans; Interleukin-8; Male; Middle Aged; Neutrophil Activation; Oncogenes; Pancreatitis

Age-related changes in human cell-specific cytokine responses to acute illness have not been well examined. We therefore evaluated age-related differences in T, B and natural killer (NK) peripheral blood lymphocyte cytokine responses of 309 acutely ill hospitalized people in Malawi, Africa, < 1 month-61 years of age. We used four-colour flow cytometry and performed Wilcoxon rank sum and Kruskal-Wallis tests, Pearson (rp) and Spearman (rs) correlations, and linear and logistic regression analyses to control for human immunodeficiency virus infection (HIV) status, the percentages of lymphocytes expressing CD4, and the nature of the acute infection. The percentages of CD8- and CD8+ T cells producing induced IL-8 decreased with age (rs = -0.44 and -0.53). The percentages of T cells producing TNF-alpha were higher, and the percentages producing IL-10 were lower, in those > or =13 than those < 13 years old (medians: 17.7 versus 10.5 and 1.4 versus 3.0, respectively). The percentages of CD8- T cells producing IFN-gamma were higher and stable in those > or =1 year old compared to infants (medians: 23.5 versus 10.4); the percentages of NK producing IFN-gamma were higher post-infancy and then declined to relatively low levels with increasing age. The percentages of T cells producing IL-2 were highest in those 5- <31 years old (median 5.6) and lowest in those > or =31 years old (median 1.9). The ratios of the percentages of T cells producing IL-4 to those producing IL-8 and to those producing IL-10 both increased with age. These data suggest that innate immunity, represented by NK IFN-gamma production, dominates in early life. A number of shifts occur after infancy and before adolescence, including a proinflammatory shift from IL-8 to TNF-gamma and a type 2 shift from IL-10 to IL-4 dominance. These findings suggest distinct age-related differences in the human response to acute illness and may be useful in directing future efforts at immunomodulatory therapies.

Topics: Acute Disease; Adolescent; Adult; Aging; B-Lymphocytes; CD3 Complex; CD8-Positive T-Lymphocytes; Child; Child, Preschool; Cytokines; Female; Humans; Infant; Infant, Newborn; Interferon-gamma; Interleukin-2; Interleukin-8; Killer Cells, Natural; Lymphocytes; Malawi; Male; Middle Aged; T-Lymphocytes, Helper-Inducer

Pancreatic periacinar myofibroblasts are considered to be therapeutic targets for the suppression of acute pancreatitis. To elucidate the mechanisms mediating the therapeutic actions of somatostatin on acute pancreatitis, we investigated how somatostatin affects the tumor necrosis factor (TNF)-alpha-induced interleukin (IL)-6 and IL-8 secretion from pancreatic myofibroblasts. Cytokine secretion was determined by enzyme-linked immunosorbent assay (ELISA) and Northern blotting. Nuclear factor (NF)-kappaB DNA-binding activity was evaluated by electrophoretic mobility shift assay (EMSAs). The expression of somatostatin receptor (SSTR) mRNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Somatostatin dose-dependently inhibited the TNF-alpha-induced IL-6 secretion. In comparison, the effects on IL-8 secretion were modest. Northern blot analysis demonstrated that somatostatin decreased the TNF-alpha-induced IL-6 mRNA expression, and that this effect was completely blocked by the somatostatin antagonist cyclo-somatostatin. Furthermore, somatostatin suppressed TNF-alpha-induced NF-kappaB activation. These cells bear SSTR subtypes 1 and 2. Somatostatin down-regulated the TNF-alpha-induced IL-6 secretion in human pancreatic periacinar myofibroblasts. These findings suggest that some of the therapeutic actions of somatostatin on acute pancreatitis might be mediated by reducing local IL-6 secretion in the pancreas.

Topics: Acute Disease; Blotting, Northern; Fibroblasts; Gene Expression Regulation; Humans; Interleukin-6; Interleukin-8; NF-kappa B; Pancreas; Pancreatitis; Receptors, Somatostatin; Somatostatin; Tumor Necrosis Factor-alpha

To investigate the role of inflammatory mediators in the pathogenesis of Lassa fever, the levels of a number of pro- and anti-inflammatory cytokines and chemokines in serum samples collected from hospitalized patients with fatal and nonfatal acute Lassa fever were compared with those from 2 control groups: patients with other febrile illnesses and uninfected individuals. Serum interleukin (IL)-8 and interferon (IFN)-inducible protein (IP)-10 levels were significantly higher in patients with acute nonfatal Lassa fever than in control subjects. In striking contrast, levels of these chemokines were low or undetectable in patients with fatal Lassa fever. IFN-gamma, IL-12, IL-6, and RANTES levels were elevated in all the febrile study groups. Tumor necrosis factor-alpha levels were not elevated in patients with fatal or nonfatal Lassa fever. These data indicate that acute nonfatal Lassa fever is associated with high levels of circulating IL-8 and IP-10 and that low levels or absence of these mediators correlates with a poor outcome.

Topics: Acute Disease; Case-Control Studies; Chemokine CCL5; Chemokine CXCL10; Chemokines, CXC; Enzyme-Linked Immunosorbent Assay; Hospitalization; Humans; Interferon-gamma; Interleukin-12; Interleukin-6; Interleukin-8; Kinetics; Lassa Fever

Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption most often provoked by drugs, by acute infections with enteroviruses, or by mercury. It is characterized by acute, extensive formation of nonfollicular sterile pustules on erythematous background, fever, and peripheral blood leukocytosis. We present clinical and immunological data on four patients with this disease, which is caused by different drugs. An involvement of T cells could be implied by positive skin patch tests and lymphocyte transformation tests. Immunohistochemistry revealed a massive cell infiltrate consisting of neutrophils in pustules and T cells in the dermis and epidermis. Expression of the potent neutrophil-attracting chemokine IL-8 was elevated in keratinocytes and infiltrating mononuclear cells. Drug-specific T cells were generated from the blood and skin of three patients, and phenotypic characterization showed a heterogeneous distribution of CD4/CD8 phenotype and of T-cell receptor Vbeta-expression. Analysis of cytokine/chemokine profiles revealed that IL-8 is produced significantly more by drug-specific T cells from patients with AGEP compared with drug-specific T cells from patients that had non-AGEP exanthemas. In conclusion, our data demonstrate the involvement of drug-specific T cells in the pathomechanism of this rather rare and peculiar form of drug allergy. In addition, they indicate that even in some neutrophil-rich inflammatory responses specific T cells are engaged and might orchestrate the immune reaction.

Topics: Acute Disease; Adult; Biopsy; CD4 Antigens; CD8 Antigens; Chemokine CCL11; Chemokine CCL5; Chemokines, CC; Cytokines; Dose-Response Relationship, Drug; Drug Eruptions; Exanthema; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunohistochemistry; Immunophenotyping; Interferon-gamma; Interleukin-4; Interleukin-5; Interleukin-8; Lymphocyte Activation; Male; Middle Aged; Receptors, Interleukin-2; Skin; T-Lymphocytes

Radiolabeled autologous leukocytes (WBCs) are the gold standard for imaging inflammatory bowel disease (IBD). For the rapid and adequate management of patients with IBD, there is need for a new agent at least as good as radiolabeled WBCs, but easier to prepare and without its inherent risks. In this study, the potential of interleukin-8 (IL-8) labeled with (99m)Tc using hydrazinonicotinamide (HYNIC) to image IBD was investigated in a rabbit model of acute colitis and compared with that of (99m)Tc-HMPAO-labeled granulocytes.. In rabbits with chemically induced acute colitis, inflammatory lesions were scintigraphically visualized after injection of either IL-8 or purified granulocytes, both labeled with (99m)Tc. Gamma camera images were acquired at 2 min and at 1, 2, and 4 h after injection. Four hours after injection, the rabbits were killed, and the uptake of the radiolabel in the dissected tissues was determined. The dissected colon was imaged and the inflammatory lesions were scored macroscopically. For each affected colon segment, the colitis index (affected colon-to-normal colon uptake ratio, CI) was calculated and correlated with the macroscopically scored severity of inflammation.. Both agents visualized the colitis within 1 h after injection. (99m)Tc-HYNIC-IL-8 images of the colonic abnormalities were more accurate and the intensity of uptake in the affected colon continuously increased until 4 h after injection, whereas no further increase 1 h after injection was noticed scintigraphically for (99m)Tc-HMPAO-granulocytes. The absolute uptake in the affected colon was much higher for IL-8 than for the radiolabeled granulocytes with the percentage injected dose per gram (%ID/g) 0.41 +/- 0.04 %ID/g and 0.09 +/- 0.05 4 %ID/g h after injection, respectively. With increasing severity, the CI at 4 h after injection for (99m)Tc-HYNIC-IL-8 was 4.4 +/- 0.6, 13.5 +/- 0.5, and 25.8 +/- 1.0; for granulocytes, the CI at 4 h after injection was 1.5 +/- 0.1, 3.4 +/- 0.2, and 6.4 +/- 0.5, respectively. The CI correlated with the severity of the inflammation (r = 0.95, P < 0.0001 for IL-8; r = 0.95, P < 0.0001 for granulocytes).. Within 1 h after injection, visualization of the extent of colonic inflammation in vivo was possible with (99m)Tc-HYNIC-IL-8 and (99m)Tc-HMPAO-granulocytes. Within 2 h after injection, (99m)Tc-IL-8 allowed a good evaluation, and within 4 h after injection, a meticulous evaluation of the severity of IBD. Although (99m)Tc-HMPAO-granulocytes were able to delineate the extent of IBD within 2 h after injection, an accurate estimation of severity of inflammation was not possible. (99m)Tc-HYNIC-IL-8 is an inflammation-imaging agent that showed promising results in this study. (99m)Tc-IL-8 can be prepared off-the-shelf and yields excellent imaging with high target-to-background ratios.

Topics: Acute Disease; Animals; Colitis; Colon; Female; Gamma Cameras; Granulocytes; Hydrazines; Interleukin-8; Niacinamide; Rabbits; Radionuclide Imaging; Radiopharmaceuticals; Technetium; Technetium Tc 99m Exametazime; Trinitrobenzenesulfonic Acid

Histamine released from dermal mast cells plays a central role in the increased vascular permeability in acute urticaria, and administration of anti-histamines usually suppresses development of wheals. Acute idiopathic urticaria, particularly a severe case, occasionally presents with acute inflammatory reactions such as low-grade fever and leukocytosis and is resistant to anti-histamines. Considering the wide spectrum of proinflammatory cytokines and chemokines that can be released from activated mast cells, some of them might be involved in the pathogenesis of urticaria. We measured plasma levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in 16 cases of severe acute urticaria. None of them showed elevated plasma levels of IL-8 or TNF-alpha. Nine out of 16 acute urticaria patients showed elevated circulating IL-6 with concomitant increases in serum CRP levels. All such patients were resistant to conventional anti-histamine treatment and required systemic steroids for complete suppression of wheal development. After subsidence of the urticaria, their elevated IL-6 and CRP levels dropped to their normal ranges. In contrast, all but one patient without elevated circulating IL-6 was successfully treated with a H1 receptor antagonist, cetirizine. The data suggest involvement of IL-6 in the pathogenesis of severe acute urticaria that is resistant to anti-histamines.

Topics: Acute Disease; Adolescent; Adult; Anti-Inflammatory Agents; Cetirizine; Enzyme-Linked Immunosorbent Assay; Female; Histamine H1 Antagonists; Humans; Interleukin-6; Interleukin-8; Male; Methylprednisolone; Middle Aged; Treatment Failure; Tumor Necrosis Factor-alpha; Urticaria

The authors have shown previously that surgical specimens from infants with acute necrotizing enterocolitis (NEC) show upregulation of inducible nitric oxide (NO) synthase (iNOS) and interferon-gamma mRNA. However, the contribution of other inflammatory cytokines such as interleukin-8 (IL-8), IL-11, and IL-12 has not been defined. Likewise, the role of GTP-cyclohydrolase, the rate-limiting enzyme in tetrahydrobiopterin synthesis, and thus NO production by iNOS is unclear. In this study, the authors sought to further define the pattern of cytokine expression seen in infants with acute NEC.. The authors measured intestinal cytokine mRNA expression by semiquantitative reverse transcriptase polymerase chain reaction in 21 infants with histologically confirmed NEC, 18 with other inflammatory conditions, and in 9 patients without intestinal inflammation. Guanosine triphosphate-cyclohydrolase (GTP-CH) activity was measured by specific enzyme assay. Univariate exact logistic regression analysis was performed to identify predictors of outcome.. IL-8 and IL-11 mRNA were upregulated in patients with acute NEC compared with those with other inflammatory conditions or those without disease; these levels returned to baseline at the time of stoma closure. Increased IL-11 mRNA decreased the likelihood of pan-necrosis (odds ratio, 0.93; P =.002). Increased IL-12 levels (but not IL-8) seemed to protect against pan-necrosis (odds ratio, 0.70; P =.06).. Local upregulation of IL-11 may represent an adaptive response designed to limit the extent of intestinal damage in NEC. Decreased IL-12 levels may contribute to the pathogenesis of NEC by allowing bacteria to escape host defenses.

Topics: Acute Disease; Analysis of Variance; Culture Techniques; Cytokines; Enterocolitis, Necrotizing; Female; Gene Expression Regulation; Genetic Markers; Guanosine Triphosphate; Humans; Immunohistochemistry; Infant; Infant, Newborn; Interleukin-11; Interleukin-12; Interleukin-8; Logistic Models; Male; Prognosis; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity; Severity of Illness Index

Examination of immunological status in patients with acute destructive pancreatitis with uncomplicated (14 patients) and complicated (infectious-inflammatory processes--18 patients) postoperative period illustrated depression of T- and B-links of immunity, reduction of absolute and relative number of TFU- and TFC-lymphocytes. All the patients demonstrated reliable elevation of phagocytic rate, phagocytic index and number of circulating immune complexes. These changes were more significant in patients with complicated postoperative period. Level of lactoferrin in patients with complicated period was by 10% higher than in patients without complications. Significant elevation of tumor necrosis factor Ia in blood was registered in patients of both groups. During all the periods of examination the level of interleukin-8 was higher in patients with complicated postoperative period than in the patients with favorable postoperative period. This interleukin-8 is a reliable marker of postoperative complications in acute destructive pancreatitis.

Topics: Acute Disease; Antigen-Antibody Complex; B-Lymphocytes; Data Interpretation, Statistical; Humans; Immune System Diseases; Immunoglobulins; Interleukin-8; Lactoferrin; Lymphocyte Count; Pancreatitis; Postoperative Period; T-Lymphocytes; Time Factors; Tumor Necrosis Factor-alpha

Thrombin is a procoagulant and proinflammatory molecule in vivo. In vitro, thrombin has been shown to induce endothelial activation, notably IL-8 secretion and adhesion molecule expression. In this study, we showed that thrombin may induce a new cascade leading from acute to chronic inflammation. Thrombin was able to induce the production of both IL-6 and monocyte chemotactic protein-1 (MCP-1) by HUVEC independently of IL-1alphabeta and TNF-alpha. Addition of physiological concentrations of exogenous soluble IL-6Ralpha (sIL-6Ralpha) to thrombin-activated HUVEC was sufficient to increase the amounts of MCP-1 produced, but not those of IL-8. These effects could be blocked by anti-IL-6 or anti-sIL-6Ralpha blocking mAb, demonstrating the existence of an autocrine loop of MCP-1 secretion, involving the IL-6/IL-6Ralpha/gp130 complex on HUVEC. In addition, we identified IL-8-activated neutrophils as a potential source of sIL-6Ralpha because IL-8 induced IL-6Ralpha shedding from the neutrophil membranes and increased in parallel sIL-6Ralpha concentrations in neutrophil supernatants. Furthermore, addition of neutrophils to thrombin-activated HUVEC significantly increased MCP-1 secretion, which could be decreased by blocking IL-6. Thus, thrombin-activated endothelium may induce a cascade of events characterized by IL-8 secretion, neutrophil local infiltration, and the release of IL-6Ralpha from neutrophil membranes. sIL-6Ralpha may then complex with IL-6 and increase the amount of MCP-1 produced by thrombin-activated endothelium, favoring monocyte infiltration, and the transformation of acute into chronic inflammation.

Topics: Acute Disease; Animals; Autocrine Communication; Blood Coagulation; Cells, Cultured; Chemokine CCL2; Chemokine CXCL1; Chemokines, CXC; Chemotactic Factors; Chemotaxis, Leukocyte; Chronic Disease; Endothelium, Vascular; Growth Substances; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-1; Interleukin-6; Interleukin-8; Macromolecular Substances; Mice; Models, Animal; Neutrophils; Receptors, Interleukin-6; Recombinant Fusion Proteins; Signal Transduction; Solubility; Thrombin; Tumor Necrosis Factor-alpha; Umbilical Veins

Previous publications demonstrated that elevated systemic levels of interleukin (IL)-8 decrease local neutrophil recruitment. We tested whether sustained, high plasma levels of IL-8 would prevent local inflammation after inflammatory insults. Mice carrying the transgene for human IL-8 were separated on the basis of their plasma levels of IL-8 into IL-8-positive (plasma levels >90 ng/ml) and IL-8-negative (IL-8 below detection). Presence of the IL-8 transgene did not improve survival or morbidity nor did it alter peritoneal neutrophil recruitment induced by the cecal ligation and puncture model of sepsis. In an acute lung injury model created by intratracheal injection of acid, IL-8-positive mice showed no reduction in alveolar neutrophil recruitment. There was no difference in the local recruitment of neutrophils when either thioglycollate or glycogen was injected intraperitoneally. We examined the chemotactic response to murine chemokines to test how neutrophil recruitment occurs in the setting of elevated plasma IL-8 and found that neutrophils from both IL-8-positive and -negative mice respond equally well to recombinant KC or macrophage inflammatory protein (MIP)-2. We measured KC and MIP-2 in the peritoneum after thioglycollate injection and demonstrated that IL-8-positive mice have significantly higher levels of the chemokines compared to the IL-8-negative mice. Antibody inhibition of KC and MIP-2 in the IL-8-positive mice significantly decreased peritoneal neutrophil recruitment in response to thioglycollate, clarifying their important role in the local neutrophil recruitment. Our data demonstrate that despite the presence of high plasma levels of IL-8, neutrophils may still be recruited to sites of local inflammation because of chemokine redundancy.

Topics: Acute Disease; Animals; Cecum; Chemokines, CXC; Glycogen; Humans; Hydrochloric Acid; Inflammation; Interleukin-8; Ligation; Lung Diseases; Mice; Mice, Transgenic; Morbidity; Neutrophil Infiltration; Peritoneum; Punctures; Reference Values; Thioglycolates; Transgenes

Activated monocytes may contribute to the pathogenesis of ischemic stroke. We tested the hypothesis that release products and procoagulant activity of monocytes are increased in acute ischemic stroke. In patients on days 1, 3 and 7 after ischemic stroke and in age- and sex-matched healthy control subjects, we assessed plasma levels of interleukin 8 (IL-8) and neopterin (enzyme linked immunosorbent assay, ELISA) and investigated superoxidanion release (ferricytochrome C reduction), procoagulant activity (one-stage clotting assay) and tissue factor (TF) gene transcription (reverse transcriptase polymerase chain reaction) by monocytes. As compared to control subjects (n=23), IL-8 levels were increased on day 1 after stroke (n=22; p=0.005) and remained elevated on days 3 and 7. Neopterin levels were elevated on days 3 and 7 (p<0.05, respectively) but not on day 1. Neopterin and IL-8 were not correlated with monocyte counts. Superoxid anion production by stimulated and unstimulated monocytes was not different between groups. TF mRNA could neither be detected in monocytes from patients investigated within 12 h after ischemia (n=12) nor in control subjects (n=10) and procoagulant activity of cells was similar in both groups. Our results indicate increased monocyte activation after ischemic stroke although not all activation parameters were elevated. We found no support for the hypothesis that circulating monocytes express TF and possess increased procoagulant activity. Elevated IL-8 may contribute to stroke pathophysiology by activating polymorphonuclear leukocyte (PMNL) activation early after ischemia.

Topics: Acute Disease; Aged; Blood Coagulation; Brain; Brain Ischemia; Female; Gene Expression; Humans; Interleukin-8; Leukocyte Count; Male; Middle Aged; Monocytes; Neopterin; RNA, Messenger; Stroke; Superoxides; Thromboplastin; Transcription, Genetic

Pro-inflammatory (IL-6, TNFalpha and IL-8) and anti-inflammatory (IL-10) cytokines were determined in weekly samples from 52 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IL-6 increased immediately after transplant peaking at week +3, but IL-8 concentrations were elevated only during week +1. After a slight decrease in week +1, TNF-alpha significantly increased from week +2 and peaked at week +3, whereas, IL-10 values started to rise in week +2 and peaked during week +4. IL-6 and TNF-alpha were positively correlated from week +2 to week +4, and IL-6 levels at week +1 were related with fever and severe stomatitis. Serum levels of IL-6 at week +1 and IL-10 at week +4 were significantly higher in patients with early transplant-related complications, such as fever, severe stomatitis or acute GVHD > or = overall grade II than in those without the complications. We conclude that a high serum IL-6 level at week +1 may be an early predictor of transplant-related complications and that it seems to trigger pro- and anti-inflammatory cytokine release. Kinetic patterns of IL-6 and IL-10 were more exaggerated in those with complications after HSCT.

Topics: Acute Disease; Adult; Biomarkers; Cytokines; Female; Fever; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Kinetics; Male; Middle Aged; Mouth Mucosa; Prognosis; Stomatitis; Transplantation, Homologous; Tumor Necrosis Factor-alpha

It has been postulated that in severely ill patients splanchnic hypoperfusion may cause endotoxin release from the gut, and this leakage of endotoxin into the circulation can trigger the cascade of inflammatory cytokines. We tested this hypothesis in 9 patients with acute severe pancreatitis by monitoring gastric intramucosal pH (pHi) as measure of splanchnic hypoperfusion at 12-h intervals trying to correlate it to endotoxin and cytokine release. Only 3 of 59 samples, obtained from 3 patients contained circulating endotoxin. Thirteen of 15 plasma samples drawn at pHi <7.20 did not contain endotoxin. The pHi was significantly lower in patients who subsequently developed 3 or more organ failures (P = 0.0017, analysis of variance). Although endotoxemia was only occasionally found, most patients had measurable interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) in their plasma. Concentrations of IL-6, IL-8, and IL-10 on admission correlated to degree of organ dysfunction as measured by the multiple organ system failure score (P = 0.035, r = 0.74; P = 0.010, r = 0.91; P = 0.021, r = 0.82, respectively). In conclusion, patients with acute, severe pancreatitis often have splanchnic hypoperfusion and produce a wide array of cytokines despite a rare occurrence of endotoxemia.

Topics: Acute Disease; Adult; APACHE; Cytokines; Endotoxins; Female; Gastric Acid; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Interleukin-10; Interleukin-6; Interleukin-8; Male; Pancreatitis; Splanchnic Circulation

Although airway inflammation is recognized as a key feature of asthma, the characteristics of airway inflammation in children with acute severe asthma are not well defined. The aim of this study was to describe the characteristics of airway inflammation in children with an acute exacerbation of asthma using sputum cell counts and fluid-phase measurements and to examine the changes in these parameters upon resolution of the exacerbation. Children (n = 38) presenting to the Emergency Department with acute asthma underwent successful sputum induction using ultrasonically nebulized normal saline (n = 22), or expectorated sputum spontaneously (n = 16). Sputum induction was repeated at least 2 wk later when the children had recovered (n = 28). Sputum portions were selected, dispersed and total and differential cell counts performed. Neutrophil elastase and EG2-positive eosinophils were assessed and fluid-phase eosinophil cationic protein (ECP), myeloperoxidase (MPO), interleukin-8 (IL-8), and IL-5 were measured. During the acute exacerbation the median (range) total cell count was 8.4 x 10(6)/ml (0.5 to 190.3), and fell significantly at resolution to 1.3 x 10(6)/ml (p < 0.01). The inflammatory cell infiltrate was mixed and included eosinophils (0.8 x 10(6)/ml), neutrophils (3.3 x 10(6)/ml), and mast cells. EG2(+) cells were high and correlated with the degree of airflow obstruction (r = -0.5, p = 0.02). They decreased significantly at resolution as did supernatant ECP (1,078 versus 272 ng/ml), suggesting that eosinophils were activated during the exacerbation. MPO was 220 ng/ ml at exacerbation and fell significantly to 1 ng/ml at resolution. Levels of IL-8 and IL-5 were elevated during the acute exacerbation and IL-8 concentrations decreased at resolution. In conclusion, airway inflammation can be studied in children with acute asthma by sputum induction. Airway inflammation is present during an acute exacerbation of asthma, and is characterized by infiltration and activation of both eosinophils and neutrophils. The heterogeneity of airway inflammation in acute asthma may influence response to corticosteroid therapy.

Topics: Acute Disease; Adolescent; Asthma; Child; Eosinophils; Female; Humans; Interleukin-8; Male; Neutrophil Infiltration; Respiratory Tract Infections; Sputum

Proinflammatory cytokines in sputum are useful markers of the activity of lung disease in cystic fibrosis (CF). Tumour necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) concentrations in sputum of 10 CF patients were determined during exacerbation and IL-8 in sputum of 48 patients at a yearly follow-up when patients were in optimal clinical condition. In 9 patients of the former group, TNF-alpha levels were increased during exacerbation. In 4 patients, the peak occurred within 2 d (median value > 1500 ng/l), whereas the remaining 5 had peak values on days 3-6 (median value 720 ng/l). IL-8 levels were > 800 microg/l in all 10 patients, and in 9 cases there was a positive correlation between IL-8 and TNF-alpha. Baseline IL-8 levels of 48 patients showed considerable variation (median 207 microg/l, range 1.5-392). There was a significant correlation between IL-8 concentrations and current colonization with either Pseudomonas aeruginosa or Staphylococcus aureus in the lower airways (p = 0.002), immunoglobulin G levels (p = 0.02) and the severity of the pathological findings shown by chest X-ray (p = 0.008). High IL-8 and TNF-alpha values correlated with symptoms of deterioration. IL-8 levels seemed to be markers of both current bacterial colonization and the degree of lung damage.

Topics: Acute Disease; Adolescent; Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Antibody Specificity; Bacterial Toxins; Biomarkers; Child; Cystic Fibrosis; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Interleukin-8; Male; Pseudomonas aeruginosa; Radiography; Respiratory Tract Infections; Sputum; Staphylococcus aureus; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

We have explored whether lipopolysaccharide (LPS, endotoxin) induces pancreatic injury on pancreatic acinar cells both in vivo and in vitro. Wistar male rats were treated with four intraperitoneal injections of 10 mg/kg LPS, and AR4-2J cells were exposed to increasing doses of LPS. Expression of pancreatitis-associated-protein (PAP) mRNA was strongly induced in AR4-2J cells exposed to LPS, while amylase mRNA was reduced. LPS also induced apoptosis and expression of TNF-alpha, IL-1beta, and IL-8 mRNA in AR4-2J cells. The in vivo effect of LPS showed structural signs of cellular damage, including numerous cytoplasmic vacuoles, severe nuclear alterations, and high expression of PAP mRNA. This study demonstrated that LPS induced pancreatic damage by directly affecting the pancreatic acinar cells. The role of LPS in the pathophysiology of acute pancreatitis may be partly due to the effect LPS has on the acinar cell.

Topics: Acute Disease; Acute-Phase Proteins; Animals; Antigens, Neoplasm; Apoptosis; Biomarkers, Tumor; Cell Line; Gene Expression; Humans; Injections, Intraperitoneal; Interleukin-1; Interleukin-8; Lectins, C-Type; Lipopolysaccharides; Male; Pancreas; Pancreatitis; Pancreatitis-Associated Proteins; Rats; Rats, Wistar; RNA, Messenger; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

Recently, there has been a great deal of interest in the role of cytokines in acute pancreatitis. Serum levels of IL-1, IL-6, and TNF-alpha have been demonstrated to be elevated in acute pancreatitis. We hypothesized that cytokines may be produced primarily by pancreatic parenchymal cells. Reasoning that ductal epithelium is the cell type most likely to be exposed to noxious stimuli in common causes of pancreatitis, such as ERCP and passage of a gallstone, we examined the response of well differentiated pancreatic ductal adenocarcinoma cell lines to stimuli known to stimulate cytokine production in other cells. CAPAN-1 and CAPAN-2 cells were incubated with endotoxin or TNF-alpha. The supernatant was assayed for production of IL-1, IL-6, and IL-8 by ELISA. The cells were assayed for activation of the transcription factor NF-kappaB by electrophoretic mobility shift assay. There was no detectable production of IL-1 by either cell line. CAPAN-1 cells had concentration-dependent production of IL-6 and IL-8 in response to both endotoxin and TNF-alpha. CAPAN-2 cells had concentration-dependent production of IL-6 and IL-8 in response to TNF-alpha. They had low level expression of IL-8 that was unaffected by any concentration of LPS, and no detectable production of IL-6 in response to LPS. These findings suggest that pancreatic duct cells may take an active part in the pathogenesis of acute pancreatitis through the production of cytokines.

Topics: Acute Disease; Adenocarcinoma; Cholangiopancreatography, Endoscopic Retrograde; Cholelithiasis; Cytokines; Epithelium; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Pancreatic Ducts; Pancreatic Neoplasms; Pancreatitis; Risk Factors; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

To determine interleukin (IL)-8 concentrations in ventricular cerebrospinal fluid from children with severe traumatic brain injury (TBI).. Prospective study.. University children's hospital.. Twenty-seven children hospitalized with severe TBI (Glasgow Coma Scale score < or =8), seven children with cerebrospinal fluid culture-positive bacterial meningitis, and twenty-four age-equivalent controls.. Placement of an intraventricular catheter and continuous drainage of cerebrospinal fluid.. Median [range] cerebrospinal fluid IL-8 concentration in children with TBI (0-12 hrs) (4,452.5 [0-20,000] pg/mL) was markedly greater than that in controls (14.5 [0-250]) (p < .0001) and equivalent to concentrations in children with meningitis (5,300 [1,510-22,000] pg/mL) (p = .33). Cerebrospinal fluid IL-8 remained increased in children with severe TBI for up to 108 hrs after injury. Univariate logistic regression analysis demonstrated an association between cerebrospinal fluid IL-8 and child abuse (p = .07) and mortality (p = .01). Multivariate analysis demonstrated a strong, independent association between cerebrospinal fluid IL-8 and mortality (p = .01).. The data are consistent with an acute inflammatory component of TBI in children and suggest an association between cerebrospinal fluid IL-8 and outcome after TBI. IL-8 may represent a potential target for anti-inflammatory therapy.

Topics: Acute Disease; Adolescent; Biomarkers; Child; Child, Preschool; Craniocerebral Trauma; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Interleukin-8; Logistic Models; Male; Meningitis, Bacterial; Prospective Studies; Time Factors

We report a case of acute eosinophilic pneumonia (AEP). Although the patient had been a habitual cigarette smoker for over 4 months, he had had not any respiratory distress. After he inhaled smoke from fireworks for 3 consecutive nights, the patient began to complain of cough, fever and dyspnea. He showed leukocytosis of 16,200/microl and hypoxemia of 58.1 torr. Chest radiograph showed bilateral infiltrates with Kerley A and B lines. The bronchoalveolar lavage fluid revealed 38.5% eosinophils. He was diagnosed as AEP. In this patient, inhaling of smoke from fireworks was clinically suspected to be associated with the induction of AEP.

Topics: Acute Disease; Adolescent; Fires; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-8; Leukocytosis; Male; Neutrophils; Pulmonary Eosinophilia; Smoke

To develop and evaluate an in vivo model to study early events in the pathogenesis of acute porcine pleuropneumonia.. Thirty-six 6- to 8-week-old pigs.. Pigs were inoculated intranasally or endotracheally with Actinobacillus pleuropneumoniae; inoculation routes were compared by evaluation of clinical signs, gross and microscopic lung lesions, hematologic changes, serum zinc, iron, and haptoglobin concentrations, and inflammatory cytokines.. The 2 inoculation routes resulted in similar findings, although intranasal inoculation caused unilateral gross lung lesions, whereas endotracheal inoculation caused bilateral gross lesions. Clinical signs of disease were observed < 2 hours after endotracheal inoculation and 6 to 8 hours after intranasal inoculation. Total WBC counts did not differ significantly after inoculation by either inoculation route, although band neutrophils increased significantly. The earliest findings associated with A pleuropneumoniae inoculation, irrespective of route, were decreased serum zinc and iron concentrations. Serum haptoglobin concentrations were significantly increased after inoculation. Inoculation induced rapid influx of macrophages into the lung and local induction of proinflammatory cytokines. Northern blot analysis of total RNA from lung tissue indicated that inoculated pigs had increased concentrations of interleukin (IL)-1beta, IL-1alpha, and IL-8; tumor necrosis factor messenger RNA concentration was not increased.. Endotracheal inoculation with A pleuropneumoniae rapidly and consistently induced diffuse bilateral pneumonia; thus, this method may be useful for the study of acute pathophysiologic changes associated with bacterial pneumonia and may provide an experimental model for testing modalities for prevention and treatment of this and other respiratory tract diseases of pigs.

Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Acute Disease; Administration, Intranasal; Animals; Antibodies, Monoclonal; Blotting, Northern; Cytokines; Disease Models, Animal; DNA Probes; Haptoglobins; Immunohistochemistry; Interleukin-1; Interleukin-8; Intubation, Intratracheal; Iron; Lung; Pleuropneumonia; RNA, Bacterial; Swine; Swine Diseases; Tumor Necrosis Factor-alpha; Zinc

Japanese encephalitis (JE) virus infection induces infiltration of neutrophils in neural as well as extraneural tissues in patients. As interleukin-8 (IL-8) has inflammatory properties, the present study was undertaken to investigate the IL-8 concentrations in cerebrospinal fluid (CSF) and serum from patients with JE and correlate them with neutrophil counts. IL-8 was measured in the CSF or serum of 30 patients with confirmed JE. The majority (92%) of the acute CSF samples showed raised levels of IL-8 with raised numbers of polymorphonuclear leucocytes. Similarly, significantly higher serum IL-8 concentrations were detected in the acute phase of illness than in convalescent JE patients or normal healthy controls. Twenty-one of 25 patients with high concentrations of IL-8 showed significantly increased neutrophil counts in acute phase sera. A gradual decline in neutrophil counts was observed in the convalescent phase of patients who recovered. There was a significant correlation between IL-8 level and the severity of illness, as all severely ill and fatal cases showed higher levels of IL-8 in acute CSF or serum than the levels found in those who recovered. IL-8 concentrations remained high for a longer period in patients with prolonged severe illness than in those who made a complete recovery.

Topics: Acute Disease; Adolescent; Adult; Child; Child, Preschool; Convalescence; Encephalitis, Japanese; Humans; Interleukin-8; Leukocyte Count; Neutrophils

Acute rejection and urinary tract infection (UTI) both increase nitric oxide synthase (NOS) activity in urine from renal transplant patients. Also, with rejection, a regulatory interplay between nitric oxide (NO) and cytokines has been suggested. Thus, measurement of the temporal changes of NOS products and cytokines in urine will provide a strategy for the diagnosis of acute rejection and for its differentiation from UTI.. Soluble interleukins (ILs) and NOS-related products, cyclic GMP (cGMP), nitrate, and nitrite were measured in 192 urine samples consecutively collected from 13 patients within the first three months of transplantation. Sixty-seven additional urine specimens were collected randomly from 24 patients for follow-up analysis of the nitrate test.. Among patients who experienced rejection, the percentage (%) binding of IL-2 increased within the first five days (P = 0.0004) after transplantation and one to five days prior to the clinical diagnosis (dx) of rejection (P = 0.02). Tumor necrosis factor-alpha, IL-6, and IL-8 increased at the time of rejection dx (P < or = 0.01). With UTI, IL-2 (P = 0.01) decreased one to five days prior to dx, and IL-10 (P = 0.003) increased one to five days after dx. Although cGMP and nitrate are dependent variables, cGMP increased (P < or =0.0009) with both rejection and UTI, and nitrate increased (P = 0.0001) with rejection and decreased (P = 0.0001) with UTI. Prior to formal dx (1 to 5 days), urine nitrate clearly differentiated rejection (3004 to 7451 micromol/L) from UTI (90 to 885 micromol/L) and controls (1059 to 3235 micromol/L). The additional 67 urines demonstrated that the sensitivity of the nitrate test for rejection and UTI was 100%.. In renal transplant patients, specific temporal changes in urine cytokine levels do occur with acute rejection and UTI, but urine nitrate levels are the most precise at differentiating rejection from UTI.

Topics: Acute Disease; Adult; Creatinine; Cyclic GMP; Cytokines; Female; Follow-Up Studies; Graft Rejection; Humans; Interleukin-10; Interleukin-2; Interleukin-6; Interleukin-8; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Predictive Value of Tests; Time Factors; Tumor Necrosis Factor-alpha; Urinary Tract Infections

The serum levels of several cytokines were determined in 94 patients with Adamantiades-Behçet's disease (ABD), aged 36.1+/-11.0 years, during the active stage (n = 75) and the inactive stage (n = 19) of the disease. A group of 75 healthy individuals matched for age and sex served as controls. Cytokine levels were determined using commercially available ELISA kits. Of the 75 patients with active disease and 19 with inactive disease, 38 (51%) and 4 (21%), respectively, and 23 healthy controls (31%) were found to have detectable levels of interleukin 8 (IL-8) in their serum (P < 0.05). Also, increased IL-8 serum levels were found in patients with active disease (median 12 pg/ml, P = 0.010) compared to patients with inactive disease (< or = 10 pg/ml) and to healthy controls (< or = 10 pg/ml). In particular, patients with oral aphthous ulcers (n = 51, 34 pg/ml) and neurological features (n = 4, 71 pg/ml) exhibited increased IL-8 levels. In contrast, there was no correlation between disease activity and the serum levels of IL-1alpha, IL-1beta, tumor necrosis factor alpha (TNF-alpha), soluble intercellular adhesion molecule-1 or basic fibroblast growth factor (bFGF). In a second set of experiments, the involvement of dermal microvascular endothelial cells in IL-8 secretion was investigated. Immortalized human dermal microvascular endothelial cells (HMEC-1 cells) were maintained for 4 h in vitro with serum from 18 ABD patients or with IL-1beta, a known stimulator of IL-8 synthesis, TNF-alpha or their combination at five- to tenfold higher concentrations than those found in the serum of ABD patients. Increased IL-8 secretion was found after incubation with ABD patients' serum (median 20 pg/ml), but IL-1beta, TNF-alpha and IL-1beta + TNF-alpha failed to induce IL-8 secretion by HMEC-1 cells (< or = 1-1.2 pg/ml) in biologically relevant concentrations. Our study showed increased IL-8 serum levels in ABD patients with active oral and neurological manifestations. Human microvascular endothelial cells may, at least partially, be responsible for the enhanced IL-8 secretion in the active stage of the disease.

Topics: Acute Disease; Adult; Behcet Syndrome; Blood; Cell Line; Central Nervous System Diseases; Cytokines; Endothelium, Vascular; Female; Fibroblast Growth Factor 2; Humans; Interleukin-8; Male; Middle Aged; Oral Ulcer

The dynamic aspects of circulating cytokines and cytokine modulators and their relationship with development of multiple organ failure (MOF) in patients with acute pancreatitis were analyzed. All cytokine and C-reactive protein levels in the circulation were higher than those in the MOF group. In particular, plasma concentrations of soluble tumor necrosis factor receptors (sTNF-RI and sTNF-RII) were significantly higher in patients with MOF than in those without even at admission. Furthermore, plasma concentrations of sTNF-Rs and interleukin-1 (IL-1) receptor antagonist (IL-1ra) were much higher than those of their counterparts, TNFalpha and IL-beta, respectively. These results suggest that the plasma concentrations of sTNF-Rs are useful predictors for the development of MOF, and actions of TNF-alpha and IL-1beta could be regulated by their modulators (soluble receptor and receptor antagonist, respectively) in the pathologic condition of severe acute pancreatitis.

Topics: Acute Disease; Adolescent; Adult; C-Reactive Protein; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Receptors, Tumor Necrosis Factor; Sialoglycoproteins; Tumor Necrosis Factor-alpha

The time course and relationship between circulating and local cytokine concentrations, pancreatic inflammation, and organ dysfunction in acute pancreatitis are largely unknown.. In a prospective clinical study, we measured the proinflammatory cytokines interleukin (IL)-1 beta, IL-6 and IL-8, the anti-inflammatory cytokine IL-10, interleukin 1 beta receptor antagonist (IL-1RA), and the soluble IL-2 receptor (sIL-2R), and correlated our findings with organ and systemic complications in acute pancreatitis. In 51 patients with acute pancreatitis admitted within 72 hours after the onset of symptoms, these parameters were measured daily for seven days. In addition, 33 aspirates from ascites and the lesser sac were measured.. Sixteen patients had mild acute pancreatitis (AP) and 35 severe AP (Atlanta classification); 18 patients developed systemic complications requiring treatment. All mediators were increased in AP. sIL-2R, IL-10, and IL-6 were significantly elevated in patients with distant organ failure. An imbalance in IL-1 beta/IL-1RA was found in severe AP and pulmonary failure. Peak serum sIL-2R predicted lethal outcome and IL-1RA was an early marker of severity. IL-6 was the best prognostic parameter for pulmonary failure.. Our results suggest that local mediator release, with a probable IL-1 beta-IL-1RA imbalance in severe cases, is followed by the systemic appearance of pro- and anti-inflammatory mediators. The pattern of local and systemic mediators in complicated AP suggests a role for systemic lymphocyte activation (triggered by local release of mediators) in distant organ complications in severe AP.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Female; Humans; Inflammation Mediators; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Prognosis; Prospective Studies; Receptors, Interleukin-1; Receptors, Interleukin-2; Severity of Illness Index

This study addresses the role of interleukin (IL)-8, a CXC-chemokine, the level of which is reported to be raised in the peripheral circulation of human immunodeficiency virus-1 (HIV-1)-infected individuals, during the induction of HIV-1 expression from latency and during cytokine-mediated HIV-1 up-regulation. IL-8 at the higher concentrations tested (> or = 100 ng/ml) was unable to induce HIV-1 expression in the chronically infected promonocytic U1 cell line, as measured by p24 antigen enzyme-linked immunosorbent assay (ELISA), whereas at lower concentrations of 1 and 10 ng/ml, constitutive HIV-1 expression was only marginally reduced. HIV-1 replication in acutely infected U937 cells was also significantly reduced by IL-8. The potent up-regulation of HIV-1 expression in U1 cells by tumour necrosis factor-alpha (TNF-alpha) remained unaffected by the addition of IL-8. HIV-1 induction by IL-1beta, IL-6 and TNF-beta, cytokines grouped here as intermediate HIV-1 inducers, was suppressed by IL-8 at concentrations of 1 and 10 ng/ml. However, IL-8 at 100 ng/ml did not significantly alter the effect of IL-1beta, synergized with IL-6 in enhancing, and marginally suppressed TNF-beta-induced HIV-1 expression. IL-8 suppressed granulocyte-macrophage colony-stimulating factor (GM-CSF) and enhanced interferon-gamma (IFN-gamma)-induced HIV-1 expression in a dose-dependent manner. Pretreatment of U1 cells with IL-8 did not alter the IL-8-mediated effects on cytokine-induced HIV-1 expression, suggesting that this chemokine exerts its effect at the time of HIV-1 induction or at a postinduction stage. Furthermore, IL-8 was itself induced by cytokines that up-regulate HIV-1 expression in U1 cells and the levels produced correlated directly with the levels of p24 antigen produced, suggesting common pathways for cytokine induction of both HIV-1 and IL-8. These results show that IL-8, typically a non-inducer, can differentially modulate HIV-1 expression in U1 cells and that this is dependent on the inducing cytokine and on the concentration of IL-8.

Topics: Acute Disease; Chronic Disease; Cytokines; Dose-Response Relationship, Immunologic; HIV Infections; HIV-1; Humans; Interleukin-8; Monocytes; U937 Cells; Virus Replication

Juvenile rheumatoid arthritis (JRA) is characterized by chronic inflammation of the joints. In the present study we demonstrate that exposure of JRA patients to a noradrenergic stressor (cold pressor test) results in enhanced LPS-induced IL-6 production by peripheral blood cells of these patients. Healthy, age-matched controls had the same rise in norepinephrine, but do not respond with changes in IL-6 production after exposure to the cold pressor test. Moreover, PBMC of patients with JRA express mRNA encoding alpha(1)-adrenergic receptors (AR), predominantly of the alpha(1d)-AR subtype. In contrast, we could not detect mRNA encoding for alpha(1)-AR in PBMC of healthy controls. The results of this study suggest that expression of alpha(1)-AR mRNA in PBMC during chronic inflammation is associated with altered responses of the immune system to stress.

Topics: Acute Disease; Adolescent; Arthritis, Juvenile; Child; Child, Preschool; Chronic Disease; Cold Temperature; DNA Primers; Female; Gene Expression; Humans; Interleukin-6; Interleukin-8; Male; Monocytes; Norepinephrine; Receptors, Adrenergic, alpha-1; RNA, Messenger; Stress, Physiological

CXC chemokines are chemotactic cytokines that specifically act on neutrophils. To obtain insight into the extent of local production of CXC chemokines during acute pyelonephritis, interleukin (IL)-8, growth-related oncogene (GRO)-alpha, and epithelial cell-derived neutrophil-activating protein (ENA)-78 were measured in urine and plasma samples from patients with culture-proven urosepsis (n=33), healthy human control subjects with sterile urine (n=31), and human volunteers intravenously injected with endotoxin (n=11). Patients had profoundly elevated urine concentrations of chemokines with no (GRO-alpha and ENA-78) or little (IL-8) elevation in plasma. Endotoxin-challenged subjects demonstrated transient increases in plasma chemokine concentrations, with no (GRO-alpha) or little (IL-8 and ENA-78) elevation in urine. Urine from patients exerted chemotactic activity toward neutrophils, which was partially inhibited by neutralizing antibodies against IL-8, GRO-alpha, or ENA-78. During urosepsis, CXC chemokines are predominantly produced within the urinary tract, where they are involved in the recruitment of neutrophils to the urinary compartment.

Topics: Acute Disease; Adult; Antibodies; Chemokine CXCL5; Chemokines, CXC; Endotoxins; Growth Substances; Humans; Interleukin-8; Neutrophil Activation; Neutrophils; Pyelonephritis

The etiologic role of bacterial pathogens isolated from sputum culture in 40 to 50% of acute exacerbations of chronic bronchitis (AECB) is controversial. If bacterial pathogens cause these AECB, they should be associated with greater neutrophilic airway inflammation than pathogen-negative exacerbations.. This hypothesis was tested by comparing levels of interleukin (IL)-8, tumor necrosis factor (TNF)-alpha, and neutrophil elastase (NE) in 81 sputum samples obtained from 45 patients with AECB. Four groups were compared. In the first three groups, nontypable Haemophilus influenzae (n = 20), Haemophilus parainfluenzae (n = 27), and Moraxella catarrhalis (n = 14) were isolated as sole pathogens, respectively. In the fourth group, only normal flora was isolated (n = 20). Paired samples, obtained from individual patients at different times, that differed in their culture results were also compared.. An outpatient research clinic at a Veterans Affairs Medical Center.. These patients were participating in a prospective, longitudinal study of the dynamics of bacterial infection in chronic bronchitis, for which they were seen in the study clinic on a monthly basis as well as when they were experiencing symptoms suggestive of AECB.. None.. H influenzae exacerbations were associated with significantly higher sputum IL-8, TNF-alpha, and NE. M catarrhalis exacerbations demonstrated significantly higher sputum TNF-alpha and NE when compared to pathogen-negative exacerbations. H parainfluenzae-associated exacerbations had an inflammatory profile similar to pathogen-negative exacerbations. Sputum elastase level distinguished bacterial from nonbacterial AECB and correlated with clinical severity of the AECB.. Increased airway inflammation associated with isolation of H influenzae and M catarrhalis supports an etiologic role of these pathogens in AECB.

Topics: Acute Disease; Aged; Aged, 80 and over; Bronchitis; Chronic Disease; Fibrinogen; Haemophilus; Haemophilus influenzae; Humans; Inflammation; Inflammation Mediators; Interleukin-8; Leukocyte Elastase; Longitudinal Studies; Male; Middle Aged; Moraxella catarrhalis; Prospective Studies; Sputum; Tumor Necrosis Factor-alpha

The role of cytokines in the development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) was studied. Serum interleukin 8 (IL-8) levels were elevated in 14 episodes and undetectable in six out of 20 episodes of ACS in 19 patients with SCD. In contrast, IL-8 levels were undetectable in the sera of 29 control patients with SCD studied during routine clinic visits or hospitalization for vaso-occlusive crises. The differences in mean IL-8 levels and the proportion of patients with detectable levels between the two groups were highly significant (P < 0.0001 and 0.04 respectively). The mean IL-8 level in bronchial fluid samples from children with ACS was also significantly higher than that in sickle cell patients undergoing elective surgery (5500 +/- 1400 pg/ml vs. 1900 +/- 470 pg/ml, P = 0.03). Granulocyte colony-stimulating factor (G-CSF) (2000 +/- 1700 pg/ml) was present in five out of six samples of bronchial fluid, but not serum, from children with ACS. All but one of the patients with ACS studied were negative for the Duffy red cell antigen, which is a receptor that binds and inactivates IL-8 and other chemokines. These findings suggest that IL-8 and G-CSF may play a role in the development of the ACS and the complications associated with it.

Topics: Acute Disease; Adolescent; Adult; Bronchoalveolar Lavage Fluid; Case-Control Studies; Chest Pain; Child; Child, Preschool; Cytokines; Duffy Blood-Group System; Female; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-8; Male; Pleural Effusion; Polymerase Chain Reaction; RNA, Messenger; Sickle Cell Trait; Syndrome

The purpose of this study was to investigate the level of IL-8 in exudates clinically obtained from normal and inflamed human dental pulp tissues so as to reveal the possible relationship between IL-8 and pulpitis.. Samples of 2 microliters of pulpal exudate from each normal or clinically diagnosed as acute or chronic pulpitis teeth was obtained by filter paper strips and IL-8 level was measured by ELISA method.. No IL-8 was detected in the samples from normal pulp, but significant amount of IL-8 appeared in inflamed pulp tissues, and the level of IL-8 in exudates of acute stage of pulpitis was higher than that of chronic stage (P < 0.01).. This study demonstrates that IL-8 is produced and accumulated in pulp inflammation and may play a role in the occurrence and development of human pulpitis.

Topics: Acute Disease; Chronic Disease; Dental Pulp; Enzyme-Linked Immunosorbent Assay; Exudates and Transudates; Humans; Inflammation Mediators; Interleukin-8; Methylcellulose; Pulpitis

The production of pro-inflammatory cytokines by monocytes in vitro has been measured in eight patients with acute fasciolosis and 15 patients in the chronic stage of the disease, before and after stimulation by excretory/secretory Fasciola antigen. Results were compared with those of a control group of 12 individuals. The monocytes from patients with acute fasciolosis produced significantly higher levels of GM-CSF, IL-8 and IL-6 as compared to controls. With chronicity, the production of these cytokines was decreased as compared to the acute stage probably due to decreased antigen level in blood. Stimulation of monocytes of healthy control with E/S Fasciola antigen was accompanied with a markedly increased production of pro-inflammatory cytokines, while monocytes from patients with acute or chronic fasciolosis revealed minimal increase in production. This denoted the importance of E/S Fasciola antigen as an activator of monocytes. A second exposure to the same antigen was accompanied with a limited response.

Topics: Acute Disease; Adolescent; Adult; Animals; Antigens, Helminth; Chronic Disease; Cytokines; Fasciola; Fascioliasis; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Inflammation; Interleukin-6; Interleukin-8; Middle Aged; Monocytes

Proinflammatory cytokines are involved in the pathogenesis of acute pancreatitis. The value of serum levels of tumor necrosis factor-alpha, interleukin-1-beta, interleukin-6, and interleukin-8 in predicting the outcome of acute pancreatitis was evaluated.. In 50 patients with acute pancreatitis, the serum concentrations of tumor necrosis factor-alpha, interleukin-1-beta, interleukin-6, interleukin-8, and C-reactive protein were determined on days 1, 2, 3, 4, and 7 after admission. Acute Physiology and Chronic Health Evaluation (APACHE II) scores were recorded on days 1, 2, and 3.. Serum concentrations of interleukin-1-beta, interleukin-6, interleukin-8, and C-reactive protein on days 1-7 were significantly higher in patients with severe pancreatitis than in patients with mild pancreatitis. Patients with severe attacks had significantly elevated serum tumor necrosis factor-alpha concentrations on days 1-3 compared with those with mild attacks, but not on days 4 and 7. The median peak value of tumor necrosis factor-alpha, interleukin-1-beta, interleukin-6, and interleukin-8 was reached on day 1, in contrast to the median peak of C-reactive protein, which was reached on day 2. Using cutoff levels of 12 pg/ml for tumor necrosis factor-alpha, 1 pg/ml for interleukin-1-beta, 400 pg/ml for interleukin-6, 100 pg/ml for interleukin-8, 12 mg/dl for C-reactive protein, and 10 for the Acute Physiology and Chronic Health Evaluation (APACHE II) score, the accuracy rates for detecting severe pancreatitis were 72%, 82%, 88%, 74%, 80%, and 72%, respectively, on day 1 and 78%, 74%, 80%, 76%, 80%, and 78%, respectively, on day 2.. Among the proinflammatory cytokines, interleukin-6 is the most useful parameter for early prediction of the prognosis of acute pancreatitis.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; APACHE; Biomarkers; C-Reactive Protein; Cytokines; Female; Humans; Inflammation Mediators; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Pancreatitis; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Tumor Necrosis Factor-alpha

Various treatment regimens and difficulties with research design are encountered with cystic fibrosis (CF) because no standard diagnostic criteria exist for defining acute respiratory exacerbations. This study evaluated the role of serial monitoring of concentrations of selected cytokines and inflammatory mediators in serum and sputum as predictors of respiratory exacerbation, as useful outcome measures for CF, and to guide therapy. Interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha), neutrophil elastase-alpha-1-protease inhibitor complex (NE complex), protein, and alpha-1-protease inhibitor (alpha-1-PI) were measured in serum and sputum collected from CF patients during respiratory exacerbations and periods of well-being. Levels of NE complex, protein, and alpha-1-PI in sputum rose during respiratory exacerbations and fell after institution of antibiotic therapy (P = 0.078, 0.001, and 0.002, respectively). Mean (+/- standard error of the mean) levels of IL-8 and TNF-alpha were extremely high in sputum (13,780 +/- 916 and 249.4 +/- 23.5 ng/liter, respectively) but did not change significantly with clinical deterioration of the patient (P > 0.23). IL-8 and TNF-alpha were generally undetectable in serum, and therefore these measures were unhelpful. Drop in forced expiratory volume in 1 s was the only clinical or laboratory parameter that was close to being a determinant of respiratory exacerbation (P = 0.055). This study provides evidence of intense immunological activity occurring continually within the lungs of adult CF patients. Measurement of cytokines and inflammatory mediators in CF sputum is not helpful for identifying acute respiratory exacerbations.

Topics: Acute Disease; Adolescent; Adult; alpha 1-Antitrypsin; Cystic Fibrosis; Disease Progression; Female; Humans; Inflammation Mediators; Interleukin-8; Leukocyte Elastase; Male; Pneumonia, Bacterial; Predictive Value of Tests; Pseudomonas Infections; Reproducibility of Results; Respiratory Function Tests; Sputum; Tumor Necrosis Factor-alpha

Patients with severe acute alcoholic hepatitis develop multiple organ failure which is associated with production of inflammatory cytokines and a poor prognosis. The aim of the present pilot study was to evaluate the effects of the BioLogic-DT sorption-suspension dialyser in patients with severe acute alcoholic hepatitis. Ten patients with encephalopathy (grade II-IV) were entered into the study, 5 received treatment with the BioLogic-DT for 6 hours daily for 3 days and 5 received conventional treatment as controls. The system was biocompatible with no adverse effects on blood pressure or platelet counts, factor V, fibrinogen or antithrombin III. No bleeding episodes were observed even with the use of small doses of heparin. After 3 days, blood ammonia was lower in the BioLogic-DT treated patients than in the controls, although blood lactate was higher. There were slight increases in plasma TNF and IL-8 during treatment over and above the higher levels present initially, possibly as a result of activation of white cells in the extracorporeal circuit. The further development of the BioLogic-DT dialyser with the addition of a plasma treatment module capable of removing cytokines would be worth evaluating in acute alcoholic hepatitis.

Topics: Acute Disease; Adult; Ammonia; Biocompatible Materials; Blood Coagulation; Cytokines; Female; Hepatic Encephalopathy; Hepatitis, Alcoholic; Humans; Interleukin-8; Lactic Acid; Liver, Artificial; Male; Middle Aged; Pilot Projects; Tumor Necrosis Factor-alpha

To establish and monitor a rabbit model of graded severity of acute pancreatitis to test the hypothesis that interleukin-8 (IL-8) and the adhesion molecule complex CD11b/CD18 are involved in the development of systemic complications in severe acute pancreatitis.. Acute pancreatitis induction in rabbits by duct ligation with or without infusion of 5.0% or 0.5% chenodeoxycholic acid or 0.9% saline. Control animals underwent laparotomy. The animals were monitored biochemically, histologically and immunohistochemically.. Increased serum levels of IL-8, tumour necrosis factor alpha (TNF-alpha), amylase and lipase were found in the chenodeoxycholic acid groups when compared with the saline, duct-ligated or control groups. Leukopenia, hypocalcaemia, and hyperglycaemia were marked in the 5.0% chenodeoxycholic acid group as compared to the saline, duct-ligated and control groups. Histologically, the 5.0% chenodeoxycholic acid group manifested a significant degree of pancreatic necrosis and neutrophil infiltration. The lungs of these animals showed acute lung injury and a significant up-regulation of CD11b/CD18. IL-8 was produced in pancreatic acinar and ductal cells. A significantly large output of ascitic fluid was seen in the 5.0% chenodeoxycholic acid group.. The rabbit models of acute pancreatitis are reliable in that enzymatic and histological evidence of acute pancreatitis with or without systemic complications developed. IL-8 is produced locally in pancreatic acinar and ductal cells and significantly increased in peripheral blood during severe but not mild pancreatitis. The expression of the adhesion molecule complex CD11b/CB18 is significantly increased in lung tissue during severe acute pancreatitis with acute lung injury. IL-8 and CD11b/CB18 are involved in the pathogenesis of severe acute pancreatitis but not of mild oedematous pancreatitis.

Topics: Acute Disease; Amylases; Animals; Ascites; CD11 Antigens; CD18 Antigens; Chenodeoxycholic Acid; Cholagogues and Choleretics; Disease Models, Animal; Hyperglycemia; Hypocalcemia; Interleukin-8; Laparotomy; Leukopenia; Ligation; Lipase; Necrosis; Neutrophils; Pancreas; Pancreatic Ducts; Pancreatitis; Rabbits; Respiratory Distress Syndrome; Sodium Chloride; Tumor Necrosis Factor-alpha; Up-Regulation

To investigate bacterial growth and inflammatory mediator release in the early stage of the immune response, a unilateral acute ascending pyelonephritis was induced in rats by intrabladder inoculation of Escherichia coli. The infected left kidney showed a significant bacterial proliferation, local production of interleukin (IL)-6 and IL-8 as detected by immunocytochemistry, and extensive destruction of renal parenchyma associated with impressive leukocyte recruitment. Inducible and constitutive nitric oxide synthases (NOS) were locally expressed, and a time-dependent increase in urinary secretion of nitric oxide (NO) was seen that could be blocked by NG-monomethyl-L-arginine. However, there was a discrepancy between the NO profile in the kidney and urine. The results demonstrate that in the early stage of acute pyelonephritis kidney tubules participate actively in the local host response by producing important inflammatory mediators and that urinary NO levels are not suitable for predicting renal NOS activity.

Topics: Acute Disease; Animals; Colony Count, Microbial; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Female; Immunohistochemistry; Inflammation Mediators; Interleukin-6; Interleukin-8; Kidney; Macrophages; Monocytes; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Pyelonephritis; Rats; Rats, Sprague-Dawley

Excessive leukocyte activation has been proposed as a key mechanism in the onset of acute pancreatitis. In this study, we assessed the systemic release of various inflammatory mediators and tried to identify differences between patients with mild and severe disease. In a prospective study, 19 patients admitted for severe acute pancreatitis were compared with 24 patients with mild pancreatitis. Serum levels of interleukin-6 (IL-6), IL-8, and IL-10 were determined at the time of admission, and on days 1, 2, and 5 after hospitalization. Severity of pancreatitis was determined according to the Atlanta criteria. IL-6 levels peaked on admission in both groups with significant differences (p < 0.05) from days 0-2. IL-8 levels increased from day 0 in severe cases, and from day 1 in mild cases, to reach a plateau between days 2 and 5; significant differences were observed on days 0 and 1. IL-10 was highest on day 0; it decreased rapidly in mild cases but stayed significantly higher from days 1 to 5 in severe cases. These findings provide new evidence on the role of mediators of the inflammatory/antiinflammatory balance in acute pancreatitis. These molecules appear to be valuable early markers of severity.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; C-Reactive Protein; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Leukocyte Elastase; Male; Middle Aged; Pancreatitis

Helicobacter pylori has been widely recognized as an important human pathogen responsible for chronic gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Little is known about the natural history of this infection since patients are usually recognized as having the infection only after years or decades of chronic disease. Several animal models of H. pylori infection, including those with different species of rodents, nonhuman primates, and germ-free animals, have been developed. Here we describe a new animal model in which the clinical, pathological, microbiological, and immunological aspects of human acute and chronic infection are mimicked and which allows us to monitor these aspects of infection within the same individuals. Conventional Beagle dogs were infected orally with a mouse-adapted strain of H. pylori and monitored for up to 24 weeks. Acute infection caused vomiting and diarrhea. The acute phase was followed by polymorphonuclear cell infiltration, interleukin 8 induction, mononuclear cell recruitment, and the appearance of a specific antibody response against H. pylori. The chronic phase was characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of the typical macroscopic follicles that in humans are considered possible precursors of MALT lymphoma. In conclusion, infection in this model mimics closely human infection and allows us to study those phases that cannot be studied in humans. This new model can be a unique tool for learning more about the disease and for developing strategies for treatment and prevention.

Topics: Acute Disease; Animals; Antibodies, Bacterial; Chronic Disease; Disease Models, Animal; Dogs; Endoscopy, Gastrointestinal; Female; Helicobacter Infections; Helicobacter pylori; Interleukin-8; Male; Mice

To characterize the local response in acute otitis media, courses of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor (TNF)alpha in middle ear fluid (MEF) of the guinea pig otitis media model induced by nonviable Haemophilus influenzae were investigated with enzyme-linked immunosorbent assay (ELISA) kits. The IL-1beta concentration in H. influenzae-inoculated ears peaked 24 hours after inoculation. The IL-8 concentration was significantly higher in H. influenzae-inoculated ears than in controls 48 and 96 hours after inoculation. The TNF-alpha concentration in H. influenzae-inoculated ears had an initial peak 6 hours after inoculation and had significant late increases 48 and 96 hours after inoculation. The results suggest that IL-1beta and TNF-alpha were produced by middle ear mucosa in the early stage of the experiment by stimulation of bacterial inoculation, which caused subsequent inflammatory cell accumulation, and that IL-8 and TNF-alpha were produced in the late stage by accumulating inflammatory cells.

Topics: Acute Disease; Animals; Antibodies, Bacterial; Cross Reactions; Disease Models, Animal; Ear, Middle; Exudates and Transudates; Guinea Pigs; Haemophilus Infections; Haemophilus influenzae; Interleukin-1; Interleukin-6; Interleukin-8; Otitis Media; Tumor Necrosis Factor-alpha

Proinflammatory cytokines like TNF-alpha and IL-8 have been thought to play a pivotal role in the propagation of severe acute pancreatitis (AP) and the development of its systemic complications, particularly acute lung injury.. To investigate the effects of pretreatment with hydrocortisone on the production of cytokines and the occurrence of acute lung injury in rabbits with AP.. AP was induced in 17 rabbits by infusion of 5% chenodeoxycholic acid into the pancreatic duct, followed by ductal ligation. The rabbits were allocated to pretreatment with subcutaneous and intravenous hydrocortisone (25 mg/kg, respectively; n = 7) or 0.9% saline (n = 10) 30 min before induction of AP. Rabbits were observed for 12 h. Serum amylase, lipase, TNF-alpha, IL-8, glucose, calcium and leukocyte count were measured every 3 h. At the end of the experimental period, ascitic fluid was collected and tissue specimens from the pancreas, lungs and kidney were obtained.. Hydrocortisone pretreatment improved survival from 40 to 100%. Serum TNF-alpha and IL-8 were lower in the hydrocortisone group than in the control group at 6 h (p = 0.006 and p < 0.001, respectively). Hydrocortisone abolished leukopenia (p < 0. 001), hyperamylasemia (p = 0.05), the occurrence of acute lung injury and reduced the volume of ascites.. Our findings suggest a role for TNF-alpha and IL-8 in mediating the progress of AP from a local disease into a systemic illness. Hydrocortisone should be tested experimentally after the induction of AP and clinically as a prophylactic measure to avoid severe AP induced by endoscopic retrograde cholangiopancreaticography.

Topics: Acute Disease; Amylases; Animals; Blood Glucose; Calcium; Female; Hydrocortisone; Interleukin-8; Leukocyte Count; Lipase; Male; Pancreatitis; Premedication; Rabbits; Respiratory Distress Syndrome; Tumor Necrosis Factor-alpha

The aim of this study was to determine whether interleukin (IL)-8 is released within the upper respiratory tract of infants during respiratory syncytial virus (RSV) bronchiolitis and whether the large number of polymorphonuclear neutrophils (PMNs) present in the respiratory tract of these infants are contributing to the inflammation through release of inflammatory mediators. Twenty-seven infants with acute bronchiolitis were recruited during one winter epidemic and 20 infant control subjects were recruited from a cohort participating in a community-based vaccine study. Samples of airways fluid were obtained using nasal lavage. The lavage fluid was spun to remove the cells, and the supernatant was stored at -70 degrees C. The supernatants were subsequently assayed for the presence of IL-8, total human neutrophil elastase (HNE) and neutrophil elastase activity. In the children with bronchiolitis compared with control infants, elevated levels of IL-8 (median (range) 1.53 (0-153) versus 0 (0-5.6) ng x mL(-1)) HNE (136 (32-694) versus 14 (0-516) ng x mL(-1)) and elastase activity (4 (1-220) versus 1 (0-339) mU x mL(-1)) were found. These results indicate that interleukin-8 is released in the upper respiratory tract in response to respiratory syncytial virus infection and suggest that polymorphonuclear neutrophil products are playing an important role in the inflammatory response to respiratory syncytial virus infection in infants with acute bronchiolitis. This contrasts with the predominantly eosinophilic response evident in atopic upper and lower respiratory tract disease.

Topics: Acute Disease; Antibodies, Viral; Biomarkers; Bronchiolitis, Viral; Humans; Infant; Infant, Newborn; Interleukin-8; Leukocyte Elastase; Nasal Lavage Fluid; Neutrophils; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory System; Retrospective Studies; Severity of Illness Index

Patients with homozygous (PiZ) alpha(1)-antitrypsin (AAT) deficiency have not only low baseline serum AAT levels (approximately 10 to 15% normal) but also an attenuated acute phase response. They are susceptible to the development of premature emphysema but may also be particularly susceptible to lung damage during bacterial exacerbations when there will be a significant neutrophil influx. The purposes of the present study were to assess the inflammatory nature of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) in subjects with AAT deficiency, to compare this with COPD patients without deficiency, and to monitor the inflammatory process and its resolution following appropriate antibacterial therapy. At the start of the exacerbation, patients with AAT deficiency had lower sputum AAT (p < 0.001) and secretory leukoprotease inhibitor (SLPI; p = 0.02) with higher elastase activity (p = 0.02) compared with COPD patients without deficiency. Both groups had a comparable acute phase response as assessed by C-reactive protein (CRP) but the AAT-deficient patients had a minimal rise in serum AAT (to < 6 microM). After treatment with antibiotics, in patients with AAT deficiency, there were significant changes in many sputum proteins including a rise in SLPI levels, and a reduction in myeloperoxidase (MPO) and elastase activity (p < 0. 005 for all measures); the sputum chemoattractants interleukin-8 (IL-8) and leukotriene B(4) (LTB(4)) fell (p < 0.01), and protein leak (sputum/serum albumin ratio) became lower (p < 0.01). The changes were rapid and within 3 d of the commencement of antibiotic therapy the biochemical markers had decreased significantly, but took a variable time thereafter to return to baseline values. In conclusion, patients with AAT deficiency had evidence of increased elastase activity at the start of the exacerbation when compared with nondeficient COPD patients which probably reflects a deficient antiproteinase screen (lower sputum AAT and SLPI). The increased bronchial inflammation at presentation resolved rapidly with 14 d of antibiotic therapy.

Topics: Acute Disease; Acute-Phase Reaction; Aged; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Bacterial Infections; Bronchi; C-Reactive Protein; Female; Humans; Inflammation Mediators; Interleukin-8; Leukotriene B4; Lung Diseases, Obstructive; Male; Middle Aged; Pancreatic Elastase; Peroxidase; Phenotype; Proteinase Inhibitory Proteins, Secretory; Proteins; Respiratory Tract Infections; Secretory Leukocyte Peptidase Inhibitor; Serine Proteinase Inhibitors; Serum Albumin; Sputum

To test the hypothesis that elevated interleukin (IL)-10 plasma concentration relative to IL-6 and IL-8 in patients with acute pancreatitis is associated with improved clinical outcome.. Case series.. University hospital surgical and intensive care unit.. Patients with mild (n = 18) and severe (n = 14) acute pancreatitis were recruited within 12 hrs of admission and studied for 5 days.. None.. The plasma concentration of IL-10 was significantly elevated in patients with severe pancreatitis during the 5 days and especially so in those who died compared with survivors on day 5 (p <.03). The ratio of IL-10/IL-6 was decreased in patients with severe pancreatitis on day 5 (p < .01). There was a significant decrease in the ratio of IL-10/IL-8, but not of IL-10/IL-6, during the first 5 days (p < .014).. The findings are consistent with the hypothesis that an increase in plasma IL-10 relative to IL-6 or IL-8 is associated with improved clinical outcome.

Topics: Acute Disease; Adult; Aged; Female; Humans; Intensive Care Units; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Predictive Value of Tests; Severity of Illness Index; Treatment Outcome

In this study we demonstrate that mice which lack the murine interleukin-8 receptor homologue exhibit enhanced resistance during the early stage of infection (1-4 days after i.v. challenge with Listeria monocytogenes). This result is surprising in that interleukin-8 and other CXC chemokines are key players in the accumulation of inflammatory neutrophils, which is thought to be critical for resistance to listeriosis. Paradoxically, some of the interleukin-8 receptor knockout mice that survived acute infection with L. monocytogenes demonstrated evidence of chronic infection with L. monocytogenes.

Topics: Acute Disease; Animals; Antigens, CD; Chronic Disease; Interleukin-8; Listeria monocytogenes; Listeriosis; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Interleukin; Receptors, Interleukin-8A; Spleen

Persistent polymorphonuclear neutrophil (PMN) recruitment to airway is thought to be an important component of continuing inflammation and progression of chronic destructive lung diseases. Although chemoattractants are required for the PMN to migrate, the nature of the chemoattractants in the airways has not yet been clarified. We therefore investigated the contribution of interleukin-8 (IL-8) and leukotriene-B4 (LTB4) to the chemotactic activity of lung secretions by inhibiting their activity using a monoclonal antibody to IL-8 and an LTB4 receptor antagonist (LY293111 sodium). Fifty-nine sputum samples obtained from 19 patients with bronchiectasis were studied. In preliminary studies the chemotactic responses to IL-8 and LTB4 were found to be additive, and we were able to remove their contribution independently with the appropriate antibody and antagonist. The chemotactic activity of the secretions was related to the macroscopic appearance (mucoid, mucopurulent, and purulent), and this appeared to be related to an increase in IL-8 contribution. Chemotactic activity was reduced by antibiotic therapy and again that seemed to relate to a reduction in the IL-8 contribution. The contributions of LTB4 were similar among the three types of sputum in varying clinical states. These data suggest that LTB4 and IL-8 are important chemotactic factors in lung secretions from such patients, although IL-8 appears to play a more important role during acute exacerbations. These results may be useful in determining therapeutic strategies for chronic destructive lung diseases in the future.

Topics: Acute Disease; Anti-Bacterial Agents; Antibodies, Monoclonal; Benzoates; Bronchiectasis; Bronchitis; Cell Movement; Chemotactic Factors; Chemotaxis, Leukocyte; Chronic Disease; Disease Progression; Female; Humans; Interleukin-8; Leukotriene B4; Male; Middle Aged; Mucus; Neutrophils; Receptors, Leukotriene B4; Reproducibility of Results; Sputum; Suppuration

The neutrophil-dominated inflammation of the lung in cystic fibrosis (CF) has traditionally been seen as a physiological response to continuous opportunistic infection. Recent studies suggest, however, that regulation of the inflammatory response itself may be altered in CF. Neutrophil migration from the bloodstream involves alterations in surface expression of the adhesion molecules L-selectin and Mac-1 (CD11b/CD18). The aim of this study was to assess neutrophil adhesion molecule expression and responsiveness in CF. Neutrophils from chronic (n = 16) and acutely infected (n = 13) CF patients and 15 normal control subjects were directly assessed by Fluorescence-activated cell sorter (FACS) analysis for surface expression of L-selectin and CD11b before and after stimulation with interleukin 8 (IL-8) or f-Met-Leu-Phe (fMLP). Neutrophils from stable (n = 5) and acutely infected (n = 5) non-CF bronchiectasis patients were also assessed. Surface upregulation of CD11b was similar in all groups. Basal levels of L-selectin were also comparable among all groups, however, when stimulated, neutrophils from both stable and acutely infected CF patients shed significantly less L-selectin than those from control subjects (p < 0.05 and p < 0.01, respectively). This decreased responsiveness was not observed in either stable or acutely infected non-CF bronchiectasis patients. These results add to the accumulating evidence suggestive of a defective inflammatory response in CF.

Topics: Acute Disease; Adolescent; Adult; Aged; Bronchiectasis; CD11 Antigens; CD18 Antigens; Cell Movement; Cell Separation; Chemotaxis, Leukocyte; Chronic Disease; Cystic Fibrosis; Female; Flow Cytometry; Gene Expression Regulation; Humans; Interleukin-8; L-Selectin; Macrophage-1 Antigen; Male; Middle Aged; N-Formylmethionine Leucyl-Phenylalanine; Neutrophil Activation; Neutrophils; Pseudomonas aeruginosa; Pseudomonas Infections; Up-Regulation

Since IL-8 and MCP-1 are chemoattractant proteins that participate in the recruitment of inflammatory cells into the arthritic joint, we examined the effects of tenidap, a new anti-inflammatory drug of the oxindole family, on IL-8 and MCP-1 expression in the joints of rabbits with acute antigen arthritis. The model was induced by injecting 5 mg/ml ovalbumin into the knees of 20 preimmunized rabbits. Animals were randomized into two groups: treated with tenidap (15 mg/kg per 12 h), or untreated. The effect of tenidap treatment was evaluated on chemokine production in synovial membranes of rabbits with arthritis and in cultured monocytic and synovial cells (SC). By immunoperoxidase staining, chemokines were localized in the synovial tissue. Chemokine messenger RNA levels in the synovial membranes and in cultured cells were analysed by reverse transcription-polymerase chain reaction (RT-PCR). At the end of the study, tenidap significantly reduced neutrophil infiltration into the joint cavity (27+/-4 x 10(6) cells/ml versus 45+/-6 x 10(6) cells/ml in untreated; P<0.05), and synovial effusion (134+/-15 microl versus 236+/-19 microl in untreated; P<0.005). Untreated rabbits showed synovial membrane up-regulation in mRNA expression of IL-8 and MCP-1 (11- and seven-fold versus healthy rabbits, respectively) that was markedly decreased by tenidap (two- and three-fold versus healthy rabbits, respectively). IL-8 and MCP-1 were localized in the synovial tissue in a perivascular pattern and areas of the interstitium and lining, mostly coinciding with cell infiltration. Tenidap also reduced the accumulation of IL-8 and MCP-1 proteins. In cultured synovial and monocytic cells, tumour necrosis factor-alpha (TNF-alpha) elicited an increase in gene expression of IL-8 (four- and nine-fold, respectively) and MCP-1 (nine- and four-fold, respectively) that was significantly reversed in both cell types by 10 microM tenidap. These results suggest that the beneficial effect of tenidap in acute antigen arthritis could be related to the down-regulation in gene expression and synthesis of IL-8 and MCP-1, two key chemokines involved in the recruitment of inflammatory cells.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens; Arthritis, Experimental; Cells, Cultured; Chemokine CCL2; Chemokines; Cyclooxygenase Inhibitors; Disease Models, Animal; Down-Regulation; Gene Expression; Indoles; Interleukin-8; Leukocytes; Oxindoles; Rabbits; RNA, Messenger; Synovial Membrane; Tumor Necrosis Factor-alpha

Neutrophilic urticaria (NU) is a histologically defined entity, but its clinical and pathogenetic aspects are poorly understood. We investigated 22 NU patients whom we identified by examining 118 biopsies of weals. The patients comprised 11 of 20 with acute urticaria, nine of 49 with chronic urticaria, one of 10 with cold urticaria and one of 10 controls undergoing prick tests. Clinically, NU patients had a shorter mean duration of disease than other urticaria patients and significantly increased erythrocyte sedimentation rate and leucocytosis. Histologically, not only neutrophil counts, but to a lesser extent also eosinophil counts and mononuclear cell infiltrates were significantly increased in lesional skin of NU, and there was more marked vasodilatation and endothelial swelling. On immunohistochemistry, increased tumour necrosis factor alpha and interleukin (IL)-3 expression was noted, compared with other urticarias, whereas IL-8 expression was only minor. These data characterize NU as an acute phase urticarial reaction associated with an intense inflammatory infiltrate and marked upregulation of some mast cell-derived cytokines.

Topics: Acute Disease; Adolescent; Adult; Aged; Biopsy; Blood Sedimentation; Eosinophils; Female; Humans; Immunohistochemistry; Interleukin-3; Interleukin-8; Leukocyte Count; Male; Mast Cells; Middle Aged; Neutrophil Activation; Neutrophils; Tumor Necrosis Factor-alpha; Urticaria

Contact lens induced acute red eye (CLARE) and contact lens induced peripheral ulcer (CLPU) are among the most common contact lens induced inflammatory reactions. Both CLARE and CLPU are characterized by corneal infiltration which indicates the presence of chemoattractants and other inflammatory mediators. The aim of this study was to characterize the cytokine and chemotactic lipid inflammatory mediator profile in the tears of people experiencing CLARE or CLPU. Cytokines IL-1 beta, IL-6, IL-8, GM-CSF and LTB4 in tears were measured by antibody sandwich and competition inhibition enzyme-linked immunosorbent assays (ELISA). Platelet activating factor-like activity was measured by a degranulation assay by measuring the release of labelled serotonin from platelets. The functional role GM-CSF and chemoattractants were determined by flow cytometry and chemotaxis. Increased levels of cytokines and chemoattractants were detected in both CLARE and CLPU tears. CLPU tears showed increased levels of LTB4 (P = 0.002) and PAF-like activity (P = 0.047) whereas CLARE tears showed increased levels of GM-CSF (P = 0.002). IL-8 (P < 0.05). LTB4 (P = 0.002) and PAF-like activity (P = 0.047) compared to control tears. Flow cytometric analysis revealed that incubation of PMN with CLARE tears increased the number of IgA receptors indicating that the GM-CSF in CLARE tears was active. Combinations of suboptimal concentrations (which were found in CLARE and CLPU tears) of IL-8 with either LTB4 or PAF significantly (P < 0.0001) enhanced the chemotactic activity for PMN compared to their individual effects. Our data highlight the possible pathophysiological roles of these inflammatory mediators in leukocyte recruitment and activation during ocular inflammatory responses. The results suggests that GM-CSF, IL-8 and LTB4 are active during corneal pathology and LTB4 or IL-8 may maintain the contact lens induced PMN response in vivo.

Topics: Acute Disease; Analysis of Variance; Cells, Cultured; Contact Lenses; Corneal Ulcer; Cytokines; Dose-Response Relationship, Drug; Flow Cytometry; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Inflammation Mediators; Interleukin-8; Keratitis; Leukotriene B4; Lipids; Neutrophil Activation; Neutrophils; Platelet Activating Factor; Receptors, Fc; Tears

Topics: Acute Disease; Biomarkers; Cytokines; Humans; Interleukin-6; Interleukin-8; Pancreatitis; Prognosis

We examined the feasibility of using induced sputum to evaluate the airway inflammatory response to natural acute respiratory virus infections. We recruited eight asthmatics and nine healthy subjects on Day 4 of a cold. Viral infection was confirmed in six of the asthmatics (influenza A or B) and six of the healthy subjects (influenza A, rhinovirus, adenovirus, respiratory syncytial virus, and coronavirus). In the subjects with confirmed virus infection, five of the asthmatics had an objective exacerbation of asthma during the cold. Their sputum on Day 4 showed a high median total cell count of 19.7 x 10(6) cells/ml with a modest neutrophilia (58. 5%) and high levels of interleukin-8 (IL-8) (16,000 pg/ml), eosinophilic cationic protein (ECP) (1,880 microgram/L) and very high levels of fibrinogen (250 mg/L). In contrast, the proportion (1.3%) and absolute number of eosinophils was low. IL-2 levels were within the normal range, whereas IL-5 and interferon gamma were under the limit of detection of the assays. In the healthy subjects with a confirmed virus infection the sputum findings were qualitatively similar but significantly less prominent. Sputum IL-8 on Day 4 was strongly correlated with neutrophils (rs = 0.8, p < 0.001). This correlation was also significant when each group was analyzed separately. On Day 21 there was a fall in the absolute number of neutrophils and in ECP and fibrinogen levels in both groups. Similar results were found in the two asthmatic and three healthy subjects with a cold of comparable severity but in whom viral infection was not confirmed. We conclude that induced sputum examination can be used to study the effects of natural colds and influenza on the airways of the lungs. The results also suggest that natural colds, on Day 4, cause neutrophilic lower airway inflammation that is greater in asthmatics than in healthy subjects. The greater inflammatory response in asthmatics may be due to the changes associated with trivial eosinophilia or to the different viruses involved.

Topics: Acute Disease; Adenoviridae; Adult; Asthma; Blood Proteins; Common Cold; Coronavirus; Eosinophil Granule Proteins; Eosinophils; Feasibility Studies; Female; Fibrinogen; Humans; Inflammation; Inflammation Mediators; Influenza A virus; Influenza B virus; Influenza, Human; Interferon-gamma; Interleukin-2; Interleukin-5; Interleukin-8; Leukocyte Count; Male; Middle Aged; Neutrophils; Respiratory Syncytial Viruses; Rhinovirus; Ribonucleases; Sputum; Status Asthmaticus

As a mediator of neurogenic inflammation and pain, we hypothesized that levels of the neuropeptide Substance P (SP) would be elevated in patients with sickle cell disease (SCD) with vaso-occlusive pain crisis. SP is a known stimulator of tumor necrosis factor-alpha (TNF-alpha) release and a promoter of interleukin-8 (IL-8), which are reported to be increased in SCD. These cytokines enhance adhesion of leukocytes to endothelium and may play a role in vaso-occlusive events. Serum levels of IL-8, TNFalpha, and SP were studied in three groups of children aged 2 to 18 years: 30 well children with SCD, 21 with SCD in pain crisis, and 20 healthy age-matched controls. Serum levels of SP were elevated in all SCD patients and were highest in patients in pain crisis. The percentage of sera with detectable levels of IL-8 (>5.0 pmol/L) was increased in SCD patients as compared with the control group. IL-8 levels were similar for well SCD patients and those with pain. TNFalpha levels were not significantly different among the three groups. In three children with SCD, SP was measured at baseline and again during pain crisis. In each case, serum levels during pain crisis were higher than they were when the patient was well. We conclude that levels of SP are high in patients with SCD and increase during pain crisis. These results imply that SP plays a prominent role in the pain and inflammation of SCD and may be a measurable laboratory marker of vaso-occlusive crisis. We speculate that neurokinin receptor antagonists may have a therapeutic potential in the treatment of crisis pain.

Topics: Acute Disease; Adolescent; Anemia, Sickle Cell; Child; Child, Preschool; Female; Humans; Interleukin-8; Ischemia; Male; Pain; Substance P; Tumor Necrosis Factor-alpha

Usually it is not possible to study the initial systemic response in patients with acute pancreatitis in the first hours after onset of the disease. We used postendoscopic retrograde pancreatography (ERP) pancreatitis as a model to study cytokine and anticytokine release in the early phase of human acute pancreatitis.. Post-ERP pancreatitis was defined as a threefold increase in serum amylase and at least two of the following clinical symptoms: abdominal pain, nausea, vomiting or peritonism 24 h after ERP. Serum levels of pro-inflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor alpha (TNF), as well as endogenous antagonistic mediators of the systemic inflammatory response such as soluble tumour necrosis factor alpha receptors p55 (TNFR p55) and p75 (TNFR p75), and IL-1-receptor antagonist (IL-1-RA) and interleukin-2-receptor (IL-2R) as indicators of lymphocyte activation were measured before and 0, 1, 4, 12, 24 and 48 h after ERP. In nine patients with acute post-ERP pancreatitis, these parameters were monitored daily until C-reactive protein (CRP) was within normal ranges and were compared to patients without pancreatitis after ERP.. IL-1beta was not detectable in five patients with and four patients without post-ERP pancreatitis. The values of the remaining patients in both groups were lower than 3.9 pg/ml. IL-8 and IL-1-RA serum concentrations peaked 12 h after ERP (132.9 and 3245.0 pg/ml respectively) compared to patients without post-ERP pancreatitis (25.8 and 389.9 pg/ml respectively). The IL-6 concentration increased to 81.6 pg/ml (8.0 pg/ml in control patients) 24 h after ERP, while the peak values for CRP were measured 72 h after ERP (164.0 versus 7.7 mg/l). IL-2R content was maximally elevated 144 h after ERP (688.8 versus 255.9 U/ml), while concentrations of TNF and its receptors showed no significant change over time.. The initial response of the cytokine network to damage of the human pancreas leading to acute pancreatitis includes the release of IL-8 and the IL-1 antagonist IL-1-RA, while IL-1beta is not found in the systemic circulation. The TNF system does not seem to be involved as indicated by the lack of detectable changes in TNF and the soluble TNFR p55 and p75 serum concentrations. Lymphocyte activation as indicated by elevated IL-2R levels occurred days after the initial trauma. Even mild post-ERP pancreatitis leads to significant systemic release of cytokines and their biological counterparts.

Topics: Acute Disease; Antigens, CD; Cholangiopancreatography, Endoscopic Retrograde; Humans; Interleukin-1; Interleukin-2; Interleukin-6; Interleukin-8; Interleukins; Pancreatitis; Prospective Studies; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type II; Tumor Necrosis Factor-alpha

Chemokines are important mediators of leucocyte chemoattraction to inflammatory sites. Previous work has shown that the expression of some chemokines is upregulated during renal transplant rejection. The objectives of the present study were to determine whether chemokine expression is increased during renal transplant rejection. Immunohistochemistry was used to localize the C-X-C (alpha) chemokine interleukin-8 (IL-8) and the C-C (beta) chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta) in 30 needle biopsies of human kidney transplants taken for diagnosis of renal dysfunction. Urine samples from transplant patients taken immediately prior to biopsy were assayed for chemokine content using enzyme-linked immunosorbent assays (ELISAs). Results from groups of patients having different clinicopathological diagnoses were then compared. All three chemokines were detected in most renal transplant biopsies showing acute cellular rejection but, although infiltrating leucocytes were often positive, staining was predominantly localized to renal tubular epithelium. Staining for MCP-1 was generally weaker than for the other chemokines, and collecting tubules were usually stained more strongly than proximal convoluted tubules. Tubular epithelial staining was also found in biopsies from patients without signs of acute cellular rejection. There were significantly higher amounts of IL-8 in the urine of patients with acute cellular rejection, even when patients with urinary tract infections were excluded, but mean titres of urinary MIP-1beta did not differ between patient groups. This was also found when titres were normalized for urine volume and creatinine levels. Production of IL-8, MCP-1 and MIP-1beta is not confined to kidney transplants showing acute cellular rejection, and may be a relatively nonspecific response of tubular epithelial cells to renal damage.

Topics: Acute Disease; Adult; Chemokine CCL2; Chemokine CCL4; Chemokines, CC; Chemokines, CXC; Epithelial Cells; Female; Graft Rejection; Humans; Interleukin-8; Kidney Diseases; Kidney Transplantation; Kidney Tubules; Macrophage Inflammatory Proteins; Male; Middle Aged; Staining and Labeling

Plasma concentrations of inflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, IL-8 and TNF alpha) were determined by ELISA in 27 patients with acute rheumatic fever (RF), 12 with only arthritis (RFA) and 15 with rheumatic heart disease (RHD), before, during and after treatment. Altogether, significant increases in TNF alpha, IL-8 and IL-6 levels were observed in the acute phase as compared to the data found during and after treatment. No significant differences were observed for the other cytokines. Elevations of one or more of the inflammatory cytokines were observed in 9 of 12 patients with RFA, and 12 of 15 with RHD. Increase of TNF alpha (6/9) and IL-8 (5/9) levels were higher in RHD patients with cardiac failure. These cytokines were below the detection limits on day 7 of treatment in all 22 patients, except in two, and in all 10 days after treatment.. These findings suggest that inflammatory cytokines, as TNF alpha, IL-8 and IL-6, may play a pathogenic role in rheumatic fever.

Topics: Acute Disease; Child; Cytokines; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Rheumatic Fever; Streptococcus pyogenes; Tumor Necrosis Factor-alpha

After acute brain injury there may be increased intracranial production of cytokines, with activation of inflammatory cascades. We have sought to determine if a transcranial cytokine gradient was demonstrable in paired sera of 32 patients requiring intensive care after acute brain injury. The difference between concentrations of IL-1 beta, IL-6, IL-8 and TNF alpha in jugular venous and arterial serum was measured on admission, and at 24, 48 and 96 h after the primary injury. There were no differences in IL-1 beta, IL-8 or TNF alpha, but median gradients of 6.7 and 11.5 pg ml-1 for IL-6 were demonstrated in the traumatic brain injury (n = 22) and subarachnoid haemorrhage (n = 10) groups, respectively (normal values in serum < 4.7 pg ml-1; P < 0.001 both groups). This suggests that there is significant production of IL-6 by intracranial cells after acute brain injury. Therapy directed towards combatting the negative effects of IL-6 may potentially benefit patients who have sustained an acute brain injury.

Topics: Acute Disease; Adolescent; Adult; Aged; Brain; Brain Injuries; Critical Care; Cytokines; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Jugular Veins; Male; Middle Aged; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha

Secretion of chemokines by epithelial cells may represent a crucial event in the pathogenesis of inflammatory bowel disease (IBD). Expression of the chemokine epithelial neutrophil-activating peptide 78 (ENA-78) was monitored in patients with IBD and normal controls.. In situ hybridizations were performed on 41 tissue specimens from 15 patients with IBD and 10 controls to detect ENA-78 messenger RNA (mRNA). Immunofluorescence stainings were used to localize ENA-78 protein.. Intestinal epithelial cells expressing ENA-78 mRNA at detectable levels are found at comparable frequencies in patients with Crohn's disease and ulcerative colitis. Tissue specimens with mild to moderate histological signs of disease activity show slightly higher frequencies of ENA-78 mRNA-expressing epithelial cells than areas with signs of severe disease activity (P = 0.14). Immunofluorescence stainings showed presence of the ENA-78 protein in > 90% of preserved epithelial cells in IBD, in control tissues, ENA-78 mRNA was not detectable, and ENA-78 protein was detectable in 0%-30% of epithelial cells.. The observations are in agreement with a role of the C-X-C chemokine ENA-78 in the pathogenesis of IBD.

Topics: Acute Disease; Adult; Amino Acid Sequence; Appendicitis; Chemokine CXCL5; Chemokines; Chemokines, CXC; Female; Fluorescent Antibody Technique; Humans; Inflammation Mediators; Inflammatory Bowel Diseases; Interleukin-8; Intestinal Mucosa; Male; Middle Aged; Reference Values; RNA, Messenger; Tissue Distribution

The development of acute respiratory distress syndrome (ARDS) during acute pancreatitis is associated with interleukin (IL)-1 and tumor necrosis factor (TNF) gene expression within the pulmonary parenchyma. Although activated pancreatic enzymes have been thought to mediate pancreatitis-induced ARDS, they are not capable of inducing cytokine production in vitro. We hypothesized that IL-1 and TNF production in the lungs is essential to the development of ARDS and is induced by a mediator released from the inflamed pancreas.. Pancreatic ascites was obtained from rats after induction of bile-salt pancreatitis, cultured, and assayed for IL-1, TNF, IL-6, IL-8, IL-10, interferon-gamma, and endotoxin. Sterile, cytokine-free ascites or saline (control) was subsequently administered intravenously (20 ml/kg) to healthy rats and to IL-1 R1 or TNF R1 knockout mice.. Animals administered intravenous ascites had a 30-fold rise in pulmonary IL-1 and TNF mRNA, as well as increased alveolar leukocytes and protein. Knockout animals devoid of active IL-1 or TNF receptors failed to develop increased alveolar protein or leukocytes.. A component of pancreatic ascites other than activated enzymes, bacteria, or inflammatory cytokines is capable of inducing ARDS in healthy animals. The mechanism appears to be directly attributable to the activity of pulmonary IL-1 and TNF.

Topics: Acute Disease; Animals; Antigens, CD; Ascites; Bile Acids and Salts; Biological Factors; Cells, Cultured; Cytokines; Interferon-gamma; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Lung; Male; Mice; Mice, Knockout; Pancreatitis; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-1; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Respiratory Distress Syndrome; Tumor Necrosis Factor-alpha

The chronic skin disease psoriasis is characterized by epidermal hyperproliferation and inflammation. The exact etiology of the disease is still unknown. At the molecular level, overexpression of growth factors and proinflammatory cytokines such as IL-8 and the corresponding receptor has been described in psoriatic plaques. On the other hand, the loss of inhibitory control mechanisms is involved in the pathogenesis of the disease, as exemplified by the reduced mRNA levels for the cell cycle inhibitor p53 found in lesional skin. Here we extend these findings to a cytokine with negative regulatory functions, IL-10. Only under certain conditions are human keratinocytes able to synthesize IL-10. In skin, pathological overexpression of IL-10 was described om atopic dermatitis. IL-10 exerts its effects via a specific receptor (IL-10R). We show here for the first time the presence and functionality of IL-10R in epidermal cells and its dramatically decreased expression in acute exanthematic psoriatic epidermis by in vitro and in situ binding studies. These results were substantiated using semiquantitative reverse transcriptase-PCR, demonstrating decreased expression of the IL-10R gene in psoriatic skin, its down-modulation by the proinflammatory cytokine IL-8, and its pharmacological induction in cultured cells. Biological responsiveness of epidermal cells toward IL-10 could also be demonstrated by a reduction of the growth rate and inhibition of IFN-gamma-induced HLA-DR expression. Our results provide the first evidence for a role of the IL-10R gene in the homeostasis of the epidermis and substantiate the concept of a loss of negative regulatory peptides as a step in the eruption of psoriasis.

Topics: Acute Disease; Cells, Cultured; DNA; Down-Regulation; Gene Expression Regulation; Glucocorticoids; HLA-DR Antigens; Humans; Interleukin-10; Interleukin-8; Keratinocytes; Polymerase Chain Reaction; Protein Binding; Psoriasis; Receptors, Interleukin; Receptors, Interleukin-10; RNA, Messenger; Up-Regulation

The local and systemic release of thromboxane A2, prostaglandin I2, leukotriene B4 (LTB4), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) were studied before and after operation in 29 patients with acute and 22 with chronic posttraumatic osteomyelitis. Twenty patients without osteomyelitis, who underwent operations for fractures of the lower extremities, served as controls. Blood and tissue samples from the osteomyelitic and control groups were collected under defined conditions and mediators were determined by radioimmunoassay (thromboxane B2, 6-keto-prostaglandin F1 alpha, LTB4) or by enzyme-linked immunosorbent assay (TNF-alpha, IL-1 beta, and IL-8). In addition, common parameters (leukocyte count, C-reactive protein, temperature) were measured. The best correlation with acute disease activity was given by TNF-alpha, IL-6, IL-8, and LTB4. Plasma levels of these mediators in acute osteomyelitis were significantly increased compared to chronic osteomyelitis and to controls, respectively. Tissue samples from osteomyelitic focus showed significantly increased levels for IL-8, IL-6, TNF-alpha, IL-1 beta, and LTB4 in acute osteomyelitis, whereas the values for TxB2 and 6-keto-prostaglandin F1 alpha were only slightly increased compared to the chronic osteomyelitis group. This study describes the local and systemic liberation of various mediators in acute and chronic posttraumatic osteomyelitis in detail for the first time and provides data for pre- and postoperative monitoring of disease activity and demonstrates new pathogenetic and therapeutic aspects of bone modulation in osteomyelitis.

Topics: Acute Disease; Adult; Case-Control Studies; Chronic Disease; Cytokines; Eicosanoids; Epoprostenol; Female; Fractures, Bone; Humans; Interleukin-6; Interleukin-8; Leukotriene B4; Male; Middle Aged; Osteomyelitis; Thromboxane A2

Interleukin-8 (IL-8) is a chemoattractant that is highly selective for neutrophils. This study was designed to investigate the presence of IL-8 in peritoneal fluid of patients with acute appendicitis. The clinical circumstances underlying the secretion of IL-8 by mesothelium and its mechanism of activation have not been defined. In an in vitro model for bacterial peritonitis the role of bacteria in activating human mesothelial cells to secrete IL-8 was studied. Cultured human mesothelium was incubated with various species of pathogenic bacteria, isolated from peritoneal exudate fluids of patients with appendicitis. The amount of IL-8 secreted by the cultured mesothelial cells was determined in an IL-8 ELISA, as IL-8 was present in the original peritoneal fluid of these patients. Peritoneal fluids from patients with a perforated appendix were found to contain a significantly higher concentration of IL-8 compared to peritoneal fluids from patients with nonperforating appendicitis (121.6 (57.8) ng/ml versus 0.2 (0.07) ng/ml, respectively; mean (SEM), P < or = 0.01). Species of Bacteroïdes and Fusobacterium necrophorum induced IL-8 secretion from cultured mesothelial monolayers to levels comparable to those found in peritoneal fluids in vivo. Heat-killed bacteria and bacterial supernatant were also able to stimulate mesothelium to secrete IL-8. The results suggest that in the early phase of bacterial peritonitis the influx of PMN is regulated by bacteria-induced IL-8 secretion by the mesothelium lining the peritoneal cavity.

Topics: Acute Disease; Appendicitis; Ascitic Fluid; Bacterial Adhesion; Bacterial Infections; Cells, Cultured; Epithelium; Humans; Interleukin-8; Lipopolysaccharides; Peritonitis

We studied paired bronchoalveolar lavage (BAL) in patients with sepsis-associated acute respiratory distress syndrome (ARDS). Patients were evaluated at one institution and underwent bronchoscopy with BAL within 48 h of the onset of ARDS. Patients were restudied with bronchoscopy and BAL after 4 d of treatment. Fifty-eight patients were initially studied, with 44 patients having follow-up bronchoscopy after 4 d. The overall 30-d survival for the ARDS group was 60%. In the initial lavage, there was no difference in the neutrophils between the survivors and nonsurvivors (survivors: 59 [0-98]%; Median [Range]; nonsurvivors: 55 [0-92]%). The follow-up lavage demonstrated a significant drop in the neutrophils for the survivors (36 [4-89]%, p < 0.002) which was not seen for the nonsurvivors (70 [26-95]%). Initial IL-8 concentrations in the BAL fluid were not significantly different between the two groups. In the follow-up lavage, there was a significant fall for the IL-8 concentrations for the survivors but not the nonsurvivors. We conclude that neutrophil influx in ARDS may rapidly resolve within a week of the onset of ARDS. The resolution of neutrophils was associated with a good prognosis.

Topics: Acute Disease; Adult; Aged; Bronchoalveolar Lavage Fluid; Bronchoscopy; Female; Humans; Interleukin-8; Lung; Male; Middle Aged; Prognosis; Respiratory Distress Syndrome; Sepsis; Survival Rate

Cell surface adhesion molecules (CAM) are important promotors of the immunoinflammatory cascade. The circulating levels of soluble intercellular adhesion molecule 1 (ICAM-1) have previously been shown to correlate with disease activity in inflammatory bowel disease. The primary aim of this study was consequently to investigate if this also applies to mucosal levels of soluble ICAM-1. We measured soluble ICAM-1 levels in intestinal biopsy specimens and the endoscopic activity of 69 patients with ulcerative colitis (UC) and 14 controls and found that the median concentration of soluble ICAM-1 was significantly higher in patients with moderately or very active UC (15.0 ng/ml) as compared to slightly active (9.8 ng/ml) and inactive UC (9.5 ng/ml) as well as controls (6.5 ng/ml) (P < 0.005). To further elucidate the interactions, two other CAM [E-selectin and vascular cellular adhesion molecule 1 (VCAM-1)], together with interleukin-8 (IL-8), IL-2 receptor (IL-2R) alpha and beta chains, were also measured. A significant trend towards higher soluble E-selectin levels in biopsies with active UC (1.8 pg/ml) as compared to inactive UC (1.3 pg/ml) and to controls (< 1.0 pg/ml) (P < 0.01) was also found. In contrast, soluble VCAM-1 was barely detectable in biopsies from two UC patients. A significant correlation was found between soluble ICAM-1 and IL-8 concentrations (r = 0.46; P < 0.0001), and between sICAM-1 and sIL-2R alpha concentrations (r = 0.69; P < 0.0001), while sIL-2R beta was not detected. This study shows that intestinal ICAM-1 and E-selectin correlate with endoscopic activity of UC and with IL-8 and IL-2R alpha levels. These mediators may be useful in monitoring mucosal inflammation in studies exploring the therapeutical potential of targeting CAM. The lack of detectable VCAM-1, which is induced only in venous endothelium is interesting. It may suggest that intestinal inflammation mainly affects arterial endothelial cells and support the theory that intestinal vasculitis is involved in the pathogenesis of inflammatory bowel disease.

Topics: Acute Disease; Adult; Aged; Cell Adhesion Molecules; Colitis, Ulcerative; Colonic Diseases, Functional; E-Selectin; Female; Humans; Interleukin-8; Male; Middle Aged; Vascular Cell Adhesion Molecule-1

Proinflammatory cytokine release was measured from peripheral blood mononuclear cells (PBMCs) isolated from six volunteers and, on admission, from 16 patients with acute pancreatitis. Tumour necrosis factor (TNF) release in patients did not differ significantly from that of volunteers, whereas both interleukin (IL) 6 and IL-8 release in patients was raised when compared with that in the volunteer group (mean(s.e.m.) IL-6 20.7(4.6) versus 9.3(1.7) ng/ml, P = 0.03; IL-8 283(40) versus 128(22) ng/ml, P = 0.04). When variation in white cell count was accounted for, IL-6 and IL-8 release but not that of TNF was significantly greater in patients with severe disease than in those with mild disease. These results point to a complex upregulation of proinflammatory cytokine release from PBMCs in patients with acute pancreatitis, components of which relate to the clinical progress of the disease.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Pancreatitis; Sex Ratio; Tumor Necrosis Factor-alpha

The aim of this study was to investigate whether bronchoalveolar lavage (BAL) and serum levels of proinflammatory cytokines discriminate between different entities of patients with acute respiratory failure. BAL and circulating concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) were measured in 74 mechanically-ventilated patients and 17 healthy controls. Patients were classified as cardiogenic pulmonary oedema (CPO), acute respiratory distress syndrome (ARDS), primary severe pneumonia (PN) and a combined group (PN+ARDS). In all patients with ARDS and/or PN, markedly elevated BAL levels of IL-6 and IL-8 were detected, which were significantly greater than levels in CPO and healthy controls. Absolute quantities and time-course of these cytokines did not differentiate between the absence and presence of lung infection, or different categories of PN. Similarly, circulating IL-6 levels were comparably elevated in patients with ARDS and/or PN, whereas circulating IL-8 concentrations were inconsistently increased. TNF-alpha was rarely detected in BAL samples, but increased serum concentrations were measured in ARDS and/or PN patients. Bronchoalveolar lavage levels of interleukin-6 and interleukin-8, but not tumour necrosis factor-alpha, and serum concentrations of interleukin-6 are consistently elevated in acute respiratory distress syndrome and/or severe pneumonia, discriminating these entities from cardiogenic pulmonary oedema. Alveolar and systemic cytokine profiles do not differentiate between acute respiratory distress syndrome in the absence of lung infection and states of severe primary or secondary pneumonia, which evidently present with comparable local and systemic inflammatory sequelae.

Topics: Acute Disease; Bacterial Infections; Bronchoalveolar Lavage Fluid; Cardiac Output, Low; Cytokines; Discriminant Analysis; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Pneumonia; Pneumonia, Bacterial; Positive-Pressure Respiration; Pulmonary Edema; Pulmonary Heart Disease; Respiratory Distress Syndrome; Respiratory Insufficiency; Survival Rate; Tumor Necrosis Factor-alpha

The detection of cytokines may elucidate the pathophysiological mechanisms that produce early systemic complications in acute interstitial (i) or necrotizing (n) pancreatitis (AP). The increase in the level of cytokines in the blood of patients with AP may correlate with the severity of the disease. In a prospective clinical trial from October 1992 to August 1993, 23 patients with AP were recruited and blood samples taken for cytokine detection by commercially available Elisa kits and C-reactive protein (CRP) by laser nephelometry. Six of 11 patients with nAP died either early (n = 1) or of late septic complications. None died of iAP. The peak of cytokine and CRP level in the first 3 days of hospitalization was used for calculation. The IL-6 concentration in the blood reached up to 2600 pg/ml in the 1st few days, depending on the severity of AP, and dropped to almost zero in the next days, independently of the clinical course. The differentiation of i- versus nAP, using a cut-off line of 600 pg/ml, was correct in 20 patients [87%, sensitivity (SE): 82%, specificity (SP): 91%, P < 0.001]. The blood levels of IL-8 reached a maximum of 1381 pg/ml in the 1st few days, depending on the severity of AP, and showed a correlation with the clinical course in the following days. The peak of IL-8 blood levels indicated correctly the severity of AP in 18 out of 23 patients using a cutoff level of 200 pg/ml (accuracy: 78%, SE: 82%, SP: 75%, P < 0.01). The CRP levels increased up to a maximum of 535 mg/l and indicated the course of AP correctly in 18 out of 22 patients (SE and SP 82%, P < 0.01). There was no correlation between cytokine blood levels and mortality. In the blood samples of five patients with i- or nAP, no TNF-alpha was detectable. The blood levels of IL-6, and to a lesser extent of IL-8 and CRP, can predict the severity and early systemic complications of AP. The excessive rise in cytokines can be explained by the stimulation of immunological cells (macrophages, lymphocytes and endothelial cells) in the course of AP, inducing early systemic complications.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; C-Reactive Protein; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Necrosis; Pancreatitis; Prognosis; Prospective Studies; Survival Rate

Cytokines activate the hypothalamic-pituitary-adrenal axis and suppress inflammation by stimulating glucocorticoid secretion. The state of adrenocortical function during acute pancreatitis and its role in this disease were determined.. Cerulein-induced pancreatitis or closed duodenal loop pancreatitis was produced in rats that had undergone adrenalectomy or sham adrenalectomy, and the serum corticosterone and interleukin 8 levels and the intensity of the pancreatitis were examined.. Serum corticosterone levels were significantly higher than basal levels in both models of experimental pancreatitis. In both models, adrenalectomy increased serum amylase and pancreatic edema and produced more severe inflammation. Adrenalectomy significantly increased mortality in animals with closed duodenal loop pancreatitis. Exogenous hydrocortisone administered to adrenalectomized animals suppressed the elevation of serum interleukin 8 levels and decreased both the severity of pancreatitis and mortality.. These results suggest that the adrenocortical function is stimulated during acute pancreatitis and that the secretion of endogenous glucocorticoids may play an important role in mitigating the progress of this disease, probably by inhibiting cytokine production.

Topics: Acute Disease; Adrenal Cortex; Adrenalectomy; Amylases; Animals; Ceruletide; Corticosterone; Disease Models, Animal; Duodenum; Glucocorticoids; Hydrocortisone; Interleukin-8; Least-Squares Analysis; Male; Pancreatitis; Rats; Rats, Wistar

We evaluated the contribution of interleukin-8 (IL-8) to the pathogenesis of idiopathic pulmonary fibrosis (IPF) by studying bronchoalveolar lavage fluid (BALF) in eight patients with IPF in the chronically progressive phase, five patients with IPF in the subacutely progressive phase, eight patients with sarcoidosis (SAR), and eight control (CTL) subjects. IL-8 levels were not increased in the BALF of the patients with IPF in the chronic phase (11.3 +/- 8.8 pg/ml), nor in that of the SAR patients (13.8 +/- 7.8 pg/ml), whereas they were increased in the BALF of patients with IPF in the subacutely progressive phase (1.93 +/- 1.10 ng/ml). We then investigated extracellular and cell-associated IL-8 in lipopolysaccharide (LPS)-stimulated BALF cells to determine the IL-8-producing potential of alveolar macrophages (AM). Following LPS stimulation of BALF cells from patients with IPF in the chronic phase, both the extracellular IL-8 in culture fluid and the cell-associated IL-8 in AM were increased as compared with those for the CTL subjects (p < 0.05 and p < 0.05, respectively). These results suggest that AM of patients with IPF are primed for IL-8 production. We conclude that IL-8 may play a role in neutrophilic alveolitis, especially during the subacute phase of IPF.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Analysis of Variance; Bronchoalveolar Lavage Fluid; Chemotaxis, Leukocyte; Chronic Disease; Escherichia coli; Female; Humans; Interleukin-8; Lipopolysaccharides; Macrophage Activation; Macrophages, Alveolar; Male; Middle Aged; Neutrophils; Pulmonary Fibrosis; Sarcoidosis, Pulmonary; Stimulation, Chemical

The aim of this study was to compare the sensitivity, specificity, and diagnostic accuracy of serum interleukin-6, interleukin-8, beta 2-microglobulin, and C-reactive protein in the assessment of the severity of acute pancreatitis using commercial kits for their respective assays. Thirty-eight patients with acute pancreatitis (25 men, 13 women, mean age 59 years, range 16-97) were studied; the diagnosis was based on prolonged upper abdominal pain associated with a twofold increase of serum lipase, and it was confirmed by imaging techniques. According to the Atlanta criteria, 15 patients had severe illness and 23 had mild disease. The four serum markers were determined in all patients on admission, as well as daily for the following five days. On the first day of the disease, the sensitivity (calculated on patients with severe pancreatitis), specificity (calculated on patients with mild pancreatitis), and the diagnostic accuracy of these serum markers for establishing the severity of acute pancreatitis were 100%, 86%, and 91% for interleukin-6 (cutoff level 2.7 pg/ml); 100%, 81% and 88% for interleukin-8 (cutoff level 30 pg/ml); 58%, 81%, and 73% for beta 2-microglobulin (cutoff level 2.1 mg/liter); and 8%, 95%, and 64% for C-reactive protein (cutoff level 11 mg/dl). The results of our study indicate that, when assayed during the first 24 hr of disease onset, interleukin-6 and interleukin-8 are better markers than beta 2-microglobulin or C-reactive protein for evaluating the severity of acute pancreatitis.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; beta 2-Microglobulin; C-Reactive Protein; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Pancreatitis; ROC Curve; Sensitivity and Specificity; Time Factors

Interleukin 8 (IL-8) mRNA was detected in peripheral leukemic cells obtained from adult T-cell leukemia patients, as well as in cultured human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines (HUT-102, MT-1, SALT-3, and SKT-1B). With the use of ELISA, IL-8 protein was also detected in the culture medium of these cells and in the extracellular fluids of patients. Furthermore, we demonstrated that the HTLV-I-derived transactivator protein, tax, could stimulate endogenous IL-8 gene expression in an uninfected T-cell line (Jurkat) and in a rheumatoid synovial cell line (E-11). Induction of IL-8 by tax at protein level was also demonstrated in transfected cells. We found that the IL-8 NF-kappa B-binding site specifically formed a complex with NF-kappa B-containing nuclear extracts from HTLV-I-infected T-cell lines and freshly isolated leukemic cells from adult T-cell leukemia patients. Finally, transfection of HTLV-I tax into Jurkat cells resulted in induction of specific binding of nuclear extracts to the NF-kappa B sequence. These results suggest that the HTLV-I tax gene may transactivate the IL-8 gene through the kappa B site in HTLV-I-infected cells and that constitutive expression of the IL-8 gene may play a role in HTLV-I-associated pathogenesis.

Topics: Acute Disease; Base Sequence; DNA Primers; Gene Expression Regulation, Neoplastic; Genes, pX; Human T-lymphotropic virus 1; Humans; In Vitro Techniques; Interleukin-8; Leukemia, T-Cell; Molecular Sequence Data; NF-kappa B; Nuclear Proteins; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured

In this study, viruria following Japanese encephalitis virus (JEV) infection in mice has been shown to appear earlier in pregnant than in normal mice with proteinuria and haematuria. This was related to the production of splenic macrophage derived neutrophil chemotactic factor (MDF) following JEV infection. Intravenous inoculation of MDF in mice resulted in leakage of cells, proteins and erythrocytes in the urine as a result of altered capillary permeability. The isolation of virus from kidney did not correlate with the shedding of virus in the urine. The histological examination of sections of kidneys showed no morphological damage; however, ultrastructural degenerative changes in the mesangial cells were observed following JEV infection. These data suggest that JEV-induced macrophage derived factor regulates the leakage of proteins, erythrocytes and cells into the urine.

Topics: Acute Disease; Animals; Antibodies, Viral; Chemotaxis, Leukocyte; Encephalitis Virus, Japanese; Encephalitis, Japanese; Female; Fluorescent Antibody Technique; Hematuria; Interleukin-8; Kidney; Mice; Pregnancy; Pregnancy Complications, Infectious; Proteinuria; Spleen

Topics: Acute Disease; Bacterial Infections; Chemotactic Factors; Chronic Disease; Granuloma; Humans; Immunity, Cellular; Interleukin-8; Malaria; T-Lymphocytes; Tuberculosis

We examined the synthesis and release of the proinflammatory cytokines macrophage inflammatory protein-1 alpha (MIP-1 alpha) and interleukin-8 (IL-8) in the context of subjects with hypersensitivity pneumonitis (HP). Subjects with acute HP were found to have alveolar macrophages that released high levels of MIP-1 alpha and IL-8, whereas control subjects had cells that released low levels of these factors. Bronchoalveolar lavage fluid from HP subjects contained low but significant levels of MIP-1 alpha and IL-8. Immunohistochemistry revealed that macrophages from acute HP subjects expressed MIP-1 alpha and IL-8 at high levels. Treatment of acute HP subjects by contact avoidance or by corticosteroids reduced the synthesis of both cytokines. Supernatants of alveolar macrophages from subjects with HP were shown to attract activated CD8+ T lymphocytes, and this activity was significantly inhibited by anti-MIP-1 alpha. MIP-1 alpha and IL-8 may be important inflammatory cytokines in the development of HP via their capacity to attract inflammatory cells (activated CD8+ T lymphocytes and neutrophils, respectively) into the airways of subjects with HP.

Topics: Acute Disease; Adult; Alveolitis, Extrinsic Allergic; Bronchoalveolar Lavage Fluid; CD8-Positive T-Lymphocytes; Chemokine CCL4; Chemotaxis, Leukocyte; Cytokines; Enzyme-Linked Immunosorbent Assay; Farmer's Lung; Female; Humans; Immunohistochemistry; Interleukin-8; Macrophage Inflammatory Proteins; Macrophages, Alveolar; Male; Middle Aged; Monokines

The role of cytokines in the pathogenesis of pneumonia is still poorly understood. In a previous study the diagnostic value of measuring blood concentrations of interleukin 6 and interferon gamma was established. In the present study the value of blood concentrations of interleukin 8, granulocyte-colony stimulating factor, and lactoferrin as markers of bacteraemic pneumonia is evaluated.. The circulating concentrations of interleukin 8 (IL-8), granulocyte-colony stimulating factor (G-CSF), and lactoferrin were measured in 14 patients with bacteraemic pneumococcal pneumonia and 49 patients with atypical pneumonia or influenza A infection using enzyme immunoassays.. Serum G-CSF concentrations were higher in the group with bacteraemic pneumococcal pneumonia, and G-CSF values correlated with the white blood cell count and levels of C-reactive protein (CRP). The levels of IL-8 were higher in the group with bacteraemic pneumococcal pneumonia than the groups with Chlamydia pneumonia, Legionella pneumonia, or influenza A infection, but there was no difference when compared with the group with Mycoplasma pneumonia. A white blood cell count of > 15 x 10(9)/l was highly suggestive of bacteraemic pneumonia. The concentrations of lactoferrin were raised in all groups except those with influenza A infection, but no difference was found between the different aetiological groups. A correlation was found between lactoferrin and white blood cell counts.. Serum G-CSF and IL-8 concentrations are potential markers of bacteraemic pneumonia.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Biomarkers; Chlamydia Infections; Cytokines; Female; Granulocyte Colony-Stimulating Factor; Humans; Influenza A virus; Influenza, Human; Interleukin-8; Lactoferrin; Legionnaires' Disease; Leukocyte Count; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Pneumonia, Pneumococcal

Topics: Acute Disease; Amino Acid Sequence; Animals; Antigens, CD; Base Sequence; Chemotaxis, Leukocyte; Dogs; Gene Expression Regulation; Gene Targeting; Humans; Infections; Inflammation; Interleukin-8; Lymphocyte Activation; Mice; Models, Molecular; Protein Conformation; Rabbits; Rats; Receptors, Interleukin; Receptors, Interleukin-8A; Sequence Alignment; Sequence Homology, Amino Acid; Signal Transduction

The relationship between urine interleukin-6 (IL-6) and interleukin-8 (IL-8)/creatinine quotients and 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy, performed within 10 days of acute first-time pyelonephritis and after 1 year, was studied in 41 children. The urine IL-6 and IL-8/creatinine quotients were also related to the urine N-acetyl-beta-D-glucosaminidase (NAG) and albumin/creatinine quotients. Presence of DMSA uptake defects, reflecting local inflammation, in children in the acute phase of pyelonephritis, were associated with elevated urine IL-6/creatinine quotients (median 27 pg/mumol); in children without DMSA changes there was no increase in quotients (median non-detectable) (P < 0.05). Persistent DMSA changes at the 1-year follow-up, probably reflecting renal scarring, were only seen in children with increased urine IL-6/creatinine quotients in the acute phase (P < 0.01). No correlation was found between urine IL-8 and DMSA uptake defects. Vesicoureteral reflux (VUR) at 6-8 weeks did not correlate with the urine cytokine levels in the acute phase. The urine excretion of NAG and albumin, reflecting renal dysfunction, was associated with values of both urine IL-6 and IL-8/creatinine quotients, but not with DMSA defects or VUR. Thus, the initial urine IL-6/creatinine quotients might be used as an indicator of risk for persistent renal damage in acute pyelonephritis.

Topics: Acetylglucosaminidase; Acute Disease; Albuminuria; Child; Child, Preschool; Creatinine; Follow-Up Studies; Humans; Infant; Infant, Newborn; Interleukin-6; Interleukin-8; Kidney; Organotechnetium Compounds; Pyelonephritis; Radionuclide Imaging; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Vesico-Ureteral Reflux

Urine and serum concentrations of interleukin (IL)-6 and IL-8 were determined in 43 women with acute pyelonephritis caused by Escherichia coli. Urine and serum samples were also collected 2 weeks after the infection and during a subsequent episode of cystitis (n = 8) or asymptomatic bacteriuria (n = 8). Concentrations of IL-6 and IL-8 were related to the expression of 5 virulence markers of E. coli and glomerular filtration rate (GFR) after pyelonephritis. Patients with acute pyelonephritis had elevated urine and serum IL-6 and IL-8 levels as compared to 37 healthy women (IL-6: p < 0.001 in both cases, and IL-8: p < 0.001 in both cases). Patients infected with E. coli producing hemolysin and/or cytotoxic necrotizing factor (CNF) had significantly higher IL-6 levels in serum during acute pyelonephritis as compared to patients infected with strains without the ability to produce these factors (p = 0.0025 and p = 0.0154, respectively). Patients who had high concentrations of IL-8 in urine during acute pyelonephritis had lower GFR at follow-up as compared to patients with lower levels of IL-8 in urine (r = -0.48, p = 0.0123). In conclusion, acute pyelonephritis is accompanied by elevated urinary and serum IL-6 and IL-8 levels. Bacteria producing hemolysin and CNF seem to induce higher concentrations of IL-6 in serum. The secretion of IL-8 from renal cells may participate in the initiation and maintenance of renal inflammation which in turn may influence renal function.

Topics: Acute Disease; Adolescent; Adult; Bacterial Toxins; C-Reactive Protein; Cytotoxins; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Fimbriae, Bacterial; Glomerular Filtration Rate; Hemolysin Proteins; Humans; Interleukin-6; Interleukin-8; Kidney; Middle Aged; Pyelonephritis; Virulence

Interleukin-6 (IL-6) and interleukin-8 (IL-8) are important mediators of the inflammatory response in serious bacterial infections. We studied the levels of these two cytokines (standardised for urinary creatinine) in the urine of infants and children during and 6 weeks after acute pyelonephritis and in non-renal febrile controls and healthy children without apparent infection. IL-6 was detected in the urine of 52% of children with pyelonephritis compared with 15% of other children (P < 0.001). The median urinary IL-6 level in acute pyelonephritis was 4 pg/mumol compared with undetectable levels in the control group (P < 0.001). IL-8 was detected in 98% of children with pyelonephritis and 42% of other children (P < 0.001). The median concentration of IL-8 was 188 pg/mumol in pyelonephritis; it was undetectable in controls (P < 0.001). IL-8 levels were higher in children less than 1 year of age (P < 0.001).

Topics: Acute Disease; Child; Child, Preschool; Female; Humans; Immunoenzyme Techniques; Infant; Interleukin-6; Interleukin-8; Male; Pyelonephritis; Recurrence

To clarify the mechanism of neutrophil infiltration in glomerulonephritis, both urinary and plasma levels of a potent neutrophil chemotactic cytokine, interleukin-8 (IL-8), were measured in 40 healthy volunteers and 96 patients with various renal diseases. The plasma IL-8 levels were less than 16 pg/ml. The urinary IL-8 levels were elevated in several renal diseases including IgA nephropathy (17 of 43), acute glomerulonephritis (4 of 6), lupus nephritis (11 of 15), purpura nephritis (2 of 4), membranoproliferative glomerulonephritis (1 of 1), and cryoglobulinemia (2 of 2). IL-8 was detected immunohistochemically in diseased glomeruli, suggesting its local production. Elevated urinary IL-8 levels during the acute phase or exacerbations were found to be decreased during spontaneous or steroid pulse therapy-induced convalescence in all patients examined. The urinary IL-8 levels were higher in patients with glomerular leukocyte infiltration than in those without infiltration. Collectively, local production of IL-8 in diseased glomeruli might be involved in the pathogenesis of the glomerular diseases and measurement of IL-8 in the urine might be useful for monitoring the glomerular diseases.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Cryoglobulinemia; Female; Glomerulonephritis; Humans; Immunoenzyme Techniques; Interleukin-8; Kidney Glomerulus; Male; Methylprednisolone; Middle Aged

Topics: Acute Disease; Adult; Biomarkers; Graft Rejection; Humans; Interleukin-8; Kidney Transplantation; Male

A novel bovine neutrophil-activating peptide, bovine ENA (boENA), was identified in the conditioned media of endotoxin-stimulated bovine monocytes and alveolar macrophages. The chemotactic peptide was purified to homogeneity from conditioned media by cation-exchange chromatography and several steps of reversed-phase high-performance liquid chromatography. The partial amino acid sequence of boENA was: VVRELRCVCLTTTPGIHPKTVSDLQVIAAGPVCSKVEVIATLKNGXXV. Its cysteine molecules are positioned identically to those of the C-X-C family of human proinflammatory peptides. BoENA shows structural (73% identity in amino acid sequence) and functional homology to human ENA-78, a product of the human type II epithelial cell line A549, as demonstrated in assays for chemotaxis, aggregation, shape change, and a rise in intracellular free calcium. The immunohistochemical identification of boENA in the hyperplastic type II alveolar epithelial cells and in pulmonary alveolar leukocytes of pneumonic bovine lungs strongly supports a role for ENA-78 in the genesis of pulmonary inflammation.

Topics: Acute Disease; Amino Acid Sequence; Animals; Cattle; Cytokines; Female; Immunohistochemistry; Interleukin-8; Macrophages; Molecular Sequence Data; Monocytes; Pneumonia; Structure-Activity Relationship

Serum levels of interleukin 8 (IL-8) were examined in eight patients with acute myeloid leukaemia during 16 courses of chemotherapy. The patients experienced 14 episodes of fever which occurred in periods with granulocyte counts < 0.5 x 10(9)/l. Febrile episodes were classified as bacteriologically defined infection (n = 6), clinically defined infection (n = 2), and unexplained fever (n = 6). IL-8 was detected in 18/25 (72%), 2/3 (67%) and 3/7 (43%) of the serum samples in the respective groups. In contrast, IL-8 was detected in 22/90 (24%) of the samples taken when no fever was present (P < 0.00003 versus bacteriologically defined infection). The median concentration of IL-8 in samples taken during febrile episodes was 194 ng/ml (range 0-6358 ng/ml) and 0 (range 0-5392 ng/ml) on days without fever (not significant). In three patients with infections caused by, respectively, Streptococcus sanguis, Acinetobacter calcoanitratus and Candida albicans, IL-8 rose to a peak levels and declined during recovery. We conclude that IL-I is released systemically during infections with gram-positive and gram-negative bacteria and Candida albicans in patients with acute myeloid leukaemia and peripheral granulocytopenia due to chemotherapy. However, IL-8 can also be detected when no sign of infection is present.

Topics: Acute Disease; Adult; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Female; Fever; Humans; Interleukin-8; Leukemia, Myeloid; Leukocyte Count; Male; Middle Aged; Opportunistic Infections

Progressive or ongoing skin necrosis after traumatic injury is well known. Experimental evidence has associated these events with neutrophil activation and secondary oxidant injury. To determine the mechanism by which neutrophils migrate to a site of injury, cytokine release from injured skin was measured.. Twenty-five skin biopsy specimens of acute partial thickness skin injuries were compared with uninjured skin of the same patient. Conditioned medium from explanted skin was assayed for tumor necrosis factor (TNF), interleukin-6 (IL-6), and IL-8.. Acute skin injury resulted in a significant release of IL-8 but not IL-6 or TNF. In eight patients gradient cytokine release was found; IL-8 levels for partial thickness burn were 26.4 ng/ml, for unburned skin adjacent to the burn were 2.1 ng/ml, and for distal normal skin were 0.2 ng/ml.. IL-8 is released from acutely injured skin; IL-6 and TNF are not. This selective release suggests a mechanism whereby neutrophils are recruited into injured tissue. These neutrophils might then induce further injury, increasing the extent of posttraumatic tissue loss.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Burns; Cells, Cultured; Chemotaxis, Leukocyte; Child; Cytokines; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Neutrophils; Skin; Tumor Necrosis Factor-alpha

Glomerular infiltration by neutrophils is a hallmark of acute glomerulonephritis. The pathophysiological role of interleukin 8 (IL-8), a potent neutrophil chemotactic cytokine (chemokine), was explored in an animal model of acute immune complex-mediated glomerulonephritis by administering a neutralizing antibody against IL-8. Repeated injection of bovine serum albumin (BSA) into rabbits caused the deposition of immune complexes consisting of BSA and rabbit IgG in glomeruli. Histological analyses revealed a small but significant number of neutrophils in glomeruli and the fusion of epithelial cell foot processes. Concomitantly, urinary levels of protein and albumin increased markedly (3.20 +/- 0.97 and 1.39 +/- 0.53 mg/h, respectively) compared with those of untreated animals (0.77 +/- 0.21 and 0.01 +/- 0.01 mg/h, respectively). Anti-IL-8 antibody treatment decreased the number of neutrophils in glomeruli by 40% and dramatically prevented the fusion of epithelial cell foot process. Furthermore, treatment with anti-IL-8 antibody completely normalized the urinary levels of protein and albumin (0.89 +/- 0.15 and 0.02 +/- 0.01 mg/h, respectively). These results indicated that IL-8 participated in the impairment of renal functions in experimental acute immune complex-mediated glomerulonephritis through activating as well as recruiting neutrophils.

Topics: Acute Disease; Albuminuria; Animals; Antibodies, Monoclonal; Antigen-Antibody Complex; Glomerulonephritis; Interleukin-8; Kidney Glomerulus; Male; Mice; Proteinuria; Rabbits

CAPD-related peritonitis was used as an in-vivo model to study Il-8 during peritoneal inflammation. Eleven episodes were studied in nine patients, who were followed on 8 consecutive days from the start of peritonitis and once after recovery (control). Il-8 was measured in dialysate (night dwells) and serum. The Il-8 time course was compared to Il-6 and TNF alpha. In addition, an in-vivo relationship between dialysate Il-8 and intraperitoneal accumulation of neutrophils was studied. A highly increased peritoneal appearance rate of Il-8 was found in the acute phase that decreased to control values during recovery. A remarkable parallelism was observed for dialysate Il-8 and Il-6 with respect to the time course and the peritoneal appearance rate. In contrast, the appearance rate of TNF alpha was much less and had a different time course. In three of four cases where the dialysate Il-8 peak occurred on day 2, the dialysate Il-6 peak still coincided with Il-8, in contrast to TNF alpha (always day 1). Dialysate Il-8 generally exceeded serum concentrations during the entire follow-up, indicating intraperitoneal Il-8 synthesis. A positive correlation was present between the dialysate Il-8 peak and the maximal number of neutrophils in dialysate. This relationship was absent for Il-6 and TNF alpha. In five of six episodes where neutrophils were quantified on both day 1 and 2, the Il-8 peak occurred simultaneously with the neutrophil peak. These findings suggest that Il-8 is involved in the recruitment of neutrophils towards the dialysate during peritonitis.

Topics: Acute Disease; Adult; Aged; Ascitic Fluid; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Kidney Diseases; Leukocytes; Male; Middle Aged; Models, Biological; Neutrophils; Peritoneal Cavity; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Time Factors; Tumor Necrosis Factor-alpha

Interleukin-8 (IL-8) elaborated by monocytes and endothelial cells is a cytokine which is responsible for adhesion of leucocytes to vascular endothelium and migration of neutrophils into the cerebrospinal fluid (CSF) from the intravascular space. The inflammation in meningitis is elicited by the cytokine release from leucocytes which encounter micro-organisms in the arachnoid or subarachnoid space. In bacterial meningitis, tumour necrosis factor (TNF), IL-1 and IL-6 are produced vigorously, and initiate and augment the inflammation in the central nervous system. In this study, utilizing a quantitative immunometric sandwich enzyme immunoassay, the concentration of IL-8 was investigated in the CSF of patients with bacterial meningitis, patients with aseptic meningitis, and patients with gastroenteritis who served as controls. The IL-8 concentration was markedly higher in the CSF of patients with bacterial meningitis (224 +/- 2.57 pg/ml; mean +/- SD) than in the CSF of patients with aseptic meningitis (less than 30 pg/ml). The IL-8 level in the CSF of patients with aseptic meningitis did not differ from that in the CSF of the patients with gastroenteritis (less than 30 pg/ml). The augmented production of IL-8 in CSF may account for the inflammation in bacterial meningitis being more severe than that in aseptic meningitis.

Topics: Acute Disease; Child; Child, Preschool; Female; Gastroenteritis; Humans; Infant; Interleukin-8; Male; Meningitis, Aseptic; Meningitis, Bacterial

Acute alcoholic hepatitis is characterized by a unique degree of liver neutrophil infiltration, often accompanied by marked peripheral neutrophilia in the absence of demonstrable bacterial or fungal infection. In this study we assayed plasma and tissue levels of a potent neutrophil activator and chemotaxin, interleukin-8, in patients with a spectrum of alcoholic liver diseases and in normal and diseased control subjects. Levels of circulating interleukin-8 were undetectable in normal subjects but highly elevated in patients with alcoholic hepatitis, particularly in those who died (geometric mean = 600 ng/L; confidence interval = 323 to 1,120 vs. geometric mean = 184 ng/L; confidence interval = 114 to 309 in survivors). Levels correlated with biochemical indicators of severe disease (bilirubin: R = 0.38; international prothrombin ratio: R = 0.28; white blood cell count: R = 0.35; creatinine: R = 0.34) and with tumor necrosis factor-alpha (R = 0.43) and soluble tumor necrosis factor receptors (p55; R = 0.59). In contrast, moderate elevations in the levels of circulating interleukin-8 were seen in alcoholic cirrhosis (geometric mean = 93 ng/L; confidence interval = 40 to 213) and in alcoholic patients undergoing alcohol withdrawal (geometric mean = 137 ng/L; confidence interval = 72 to 259). Levels in nonalcoholic inflammatory liver disease were comparatively low (geometric mean = 17 ng/L; confidence interval = 10 to 29).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Autoimmune Diseases; Female; Hepatic Encephalopathy; Hepatitis; Hepatitis, Alcoholic; Humans; Immunohistochemistry; Interleukin-8; Liver; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Male; Neutrophils; Prospective Studies; Tumor Necrosis Factor-alpha

Purified leukemic cells from 30 acute myeloid leukemia (AML) cases at diagnosis were investigated for the presence of interleukin 8 (IL-8) mRNA by Northern blot analysis. IL-8 specific transcripts were detected in uncultured blasts in 14/30 cases, 10/14 from patients with M4-M5 and 4/14 from cases with M0-M3 morphology. The transcript expression was associated with the detection of IL-8 molecule in blast cells by immunostaining performed on cytospin preparations. After 24-hour culture, a strong up-regulation or the appearance in cases negative before culture of IL-8 mRNA was observed in all cases tested, and culture supernatants contained high amounts of IL-8. Our data demonstrate that leukemic cells in AML are equipped with the functional apparatus for IL-8 production. Since IL-8 displays a wide range of biological activities, including the regulation of some membrane molecules relevant to adhesion and migration processes, its production by AML blasts might be of relevance for the pattern of leukemic growth.

Topics: Acute Disease; Cell Division; Gene Expression; Humans; Interleukin-8; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Promyelocytic, Acute; RNA, Messenger; Tumor Cells, Cultured

It has been suggested that leucocytes play an important role in the pathogenesis of complicated pancreatitis. Indeed, increased plasma concentrations of neutrophil elastase as a marker of neutrophil activation could be detected in patients with a severe course of the disease. Recently, interleukin-8 (IL-8) has been described as a novel neutrophil activating peptide. To determine the role of IL-8 in acute pancreatitis we measured its serum concentrations by a specific enzyme-linked immunosorbent assay in 10 patients with acute pancreatitis daily during the first week of hospitalization. IL-8 levels were compared with plasma concentrations of neutrophil elastase and the clinical course of the disease. Three of the patients had uncomplicated pancreatitis, while seven showed various extrapancreatic complications. Patients with complicated pancreatitis had statistically significant (P less than 0.05) higher mean values of IL-8 (121 +/- 41 pg/ml-1 vs. 13 +/- 6 pg ml-1, mean +/- SEM) and neutrophil elastase (547 +/- 35 ng ml-1 vs. 250 +/- 20 ng ml-1) than patients with uncomplicated disease. There was a positive correlation (r = 0.52, P less than 0.0001) between IL-8 and neutrophil elastase in the lower concentration range of IL-8 (less than 100 pg ml-1). At IL-8 levels greater than 100 pg ml-1 neutrophil elastase was always greatly elevated; however, under these conditions the relationship between IL-8 and elastase was no longer linear. No measurable IL-8 concentrations were found when plasma elastase was less than 200 ng ml-1. During follow-up, initially elevated IL-8 concentrations decreased in correlation with clinical improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Female; Humans; Interleukin-8; Male; Middle Aged; Neutrophils; Pancreatic Elastase; Pancreatitis

Topics: Acute Disease; Cell Movement; Humans; Inflammation; Interleukin-8; Membrane Glycoproteins; Neutrophils

The evolution of acute inflammation from initiation through resolution is associated with the changing character of the infiltrating leukocytes. Recruitment of these leukocytes is dependent upon the generation of chemotactic factors that have either global or specific activity for a particular leukocyte. In this manuscript we present data demonstrating that human neutrophils can express mRNA for neutrophil chemotactic factor/interleukin 8 (IL-8), but fail to express mRNA for monocyte chemotactic protein (MCP-1). The expression of IL-8 was observed upon adherence or in response to stimulation with lipopolysaccharide. Maximal IL-8 antigenic production was noted at 24 hrs. These studies demonstrate a disparate expression of chemotactic cytokines by neutrophils.

Topics: Acute Disease; Base Sequence; Chemokine CCL2; Chemotactic Factors; Enzyme-Linked Immunosorbent Assay; Epitopes; Gene Expression; Humans; Inflammation; Interleukin-8; Lipopolysaccharides; Molecular Sequence Data; Neutrophils; RNA, Messenger

Intraalveolar leukocytosis is integral in initiating and perpetuating airspace inflammatory reactions. We used intratracheal instillation of silica suspensions in adult male rats to cause neutrophil flux (32% increase over saline controls) without creating a protein leak, so simulating an early inflammatory response. We examined the in vivo effects of a known phospholipase A2 inhibitor (mepacrine) and the two mast cell active agents (cyproheptadine and reserpine) on lung lavage fluid chemotactic capability, alveolar macrophage (AM) production of chemotactic factor(s), and neutrophil diapedesis. Only mepacrine significantly depressed the leukocytosis (from 32% to 8% of total cells), with a similar diminution in AM chemotaxin production. Separate in vitro experiments using mepacrine-pretreated neutrophils and macrophages gave evidence that mepacrine: (1) diminishes neutrophil response to chemotaxin(s), (2) inhibits spontaneous, random neutrophil movement, and (3) diminishes macrophage-derived chemotactic factor production. These observations suggest that the earliest events in alveolar inflammatory reactions probably involve local production of chemotactic factors by AM, and that mepacrine's anti-inflammatory action results from inhibitory influences on both macrophage and neutrophil populations.

Topics: Acute Disease; Animals; Cell Movement; Chemotactic Factors; Instillation, Drug; Interleukin-8; Lung Diseases; Male; Mast Cells; Neutrophils; Quinacrine; Rats; Rats, Inbred F344; Silicon Dioxide; Trachea

The characteristic histopathological features of acute alcoholic hepatitis include hyaline degeneration of hepatic parenchymal cells (Mallory bodies), hepatocellular necrosis, and granulocyte infiltration of the liver. The chemotactic response of neutrophils to highly purified Mallory bodies was studied. Mallory bodies, per se, were not chemotactic for granulocytes, nor did they generate chemotactic factors when incubated with serum. However, a factor(s) chemotactic for both granulocytes and mononuclear cells was generated when Mallory bodies were incubated with mononuclear cells, both from patients with alcoholic hepatitis or from normal controls. It was concluded that Mallory bodies stimulate peripheral blood mononuclear cells to release a factor chemotactic for granulocytes and mononuclear cells. This factor may be important in the etiology of the cellular infiltration in the livers of patients with alcoholic hepatitis.

Topics: Acute Disease; Adult; Cell Movement; Cell Separation; Chemotactic Factors; Endoplasmic Reticulum; Female; Hepatitis, Alcoholic; Humans; Interleukin-8; Lymphocytes; Male; Middle Aged; Molecular Weight; Monocytes; Peptide Hydrolases