interleukin-8 and Pancreatitis

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

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

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

Epithelial neutrophil-activating protein 78 (ENA-78) is a member of the CXC chemokines and acts as a potent chemoattractant and activator of neutrophil function. On stimulation in vitro, ENA-78 is highly expressed in many cell types. ENA-78 protein levels are strongly elevated in synovial fluid and blood of patients with rheumatoid arthritis. By in situ hybridization and immunofluorescence staining, ENA-78 has been recognized as a major CXC chemokine expressed in epithelial cells of the intestinal mucosa of patients with Crohn's disease, ulcerative colitis, and acute appendicitis. A high expression of ENA-78 and interleukin-8 (IL-8) was also observed in the exocrine tissue of patients with chronic pancreatitis (CP). It is interesting to note that expression of IP-10, MIP-1alpha, and MCP-1 is high in healthy pancreatic tissue but low in tissue of patients with CP, suggesting a mutually exclusive expression of the ELR-CXC vs. non-ELR-CXC/CC chemokines. High-resolution studies of intracellular chemokines has revealed specific immunoreactivity for ENA-78 associated with the endoplasmic reticulum of many cell types. In contrast, GROalpha immunoreactivity was exclusively localized in the nucleus. Despite their common effects on neutrophil functions, the differential intracellular localization of ENA-78 and GROalpha suggests additional roles for these two chemokines in normal cell biology.

Topics: Arthritis, Rheumatoid; Chemokine CXCL5; Chemokines, CXC; Chronic Disease; Humans; Inflammatory Bowel Diseases; Interleukin-8; Monocytes; Pancreatitis; Respiratory Distress Syndrome

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

Endoscopic retrograde cholangiopancreatography (ERCP) is a minimally invasive technique widely used to diagnose and treat pancreatic and biliary diseases; however, it is linked with imminent hyperamylasemia and post-ERCP pancreatitis (PEP). Somatostatin and indomethacin are the classic recommended drugs used for PEP prevention.. To elucidate the effects of somatostatin and indomethacin mono or in combination to prevent hyperamylasemia and PEP in high-risk individuals.. Altogether 1458 patients who underwent ERCP in our hospital from January 2016 to May 2022 were included in this investigation and categorized into 4 groups based on the treatment regimen: placebo, indomethacin, somatostatin, and indomethacin + somatostatin. The pre operation and post operation (at 6, 12, and 24 h) hospitalization cost, length of stay, the occurrence of hyperamylasemia and PEP, levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, and VAS pain score were determined in the 4 groups. In all the groups, VAS and IL-6, TNF-α, and IL-8 levels substantially increased in the pretreatment and decreased sequentially from 6 to 24 h post operation. The individuals in the indomethacin revealed substantially reduced hyperamylasemia, VAS, and levels of IL-6, TNF-α, and IL-8, 6 h post operation, whereas the hospitalization fee, length of stay, PEP incidence, VAS, levels of IL-6, TNF-α, and IL-8, 12 and 24 h post operation were not statistically important in comparison with the individuals who received placebo therapy. The somatostatin and the indomethacin + somatostatin groups indicated markedly alleviated hospitalization fee, length of stay, the occurrence of hyperamylasemia and PEP, VAS, and the levels of IL-6, TNF-α, and IL-8 at 6, 12, and 24 h post operation compared with the placebo cohort. Furthermore, compared with the indomethacin group, the above-determined factors notably reduced at 6, 12, and 24 h post operation in somatostatin and indomethacin + somatostatin groups. It was also observed that the indomethacin + somatostatin group has substantially decreased the occurrence of hyperamylasemia, VAS score, and levels of IL-6, TNF-α, and IL-8, 6 hours post operation, while at 12 and 24 h post operation, the hospitalization fee, length of stay and incidence of PEP, VAS, levels of IL-6, TNF-α, and IL-8 were not statistically important compared with the somatostatin group. It is also worth noting that the side effects of both drugs are rare and mild.. For high-risk PEP patients, indomethacin and somatostatin can efficiently alleviate post-operative hyperamylasemia and improve their life standard within 6 hours and 24 hours, respectively. Indomethacin is suitable for individuals who underwent simple, short-duration ERCP with expected mild post-operative abdominal pain, whereas somatostatin is given to patients with complicated, long-duration ERCP and expected severe post-operative abdominal pain. Their combinational therapy produces a synergistic effect and can reduce the incidence of hyperamylasemia, thereby improving patients' quality of life within 6 h and is also effective against individuals who received a more complicated, longer-duration ERCP and were expected to have severer and longer post-operative abdominal pain.

Topics: Abdominal Pain; Cholangiopancreatography, Endoscopic Retrograde; Humans; Hyperamylasemia; Indomethacin; Interleukin-6; Interleukin-8; Pancreatitis; Quality of Life; Risk Factors; Somatostatin; 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

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

The aim of this study was to evaluate the efficacy of early continuous veno-venous hemofiltration (CVVH) in decreasing the intra-abdominal pressure (IAP) and serum interleukin-8 (IL-8) level in severe acute pancreatitis (SAP) patients with abdominal compartment syndrome (ACS).. Twenty-five ACS patients of SAP were enrolled in a prospective study conducted according to the standard management protocol. They were treated in the intensive care unit (ICU) of Affiliated Yidu Central Hospital of Weifang Medical College and underwent CVVH. Eleven patients were set up as the control group that received no hemofiltration and surgical treatment due to economic or other reasons but solely conventional treatment. Serum amylase, liver and kidney function, and C reactive protein were investigated before and after treatment. IAP and blood level of IL-8 were measured daily to investigate their time course of changes and the correlation between the 2 parameters.. Serum amylase levels, C-reactive protein and IAP were significantly lower and liver and kidney function was significantly better than those of the control group (p < 0.05). IAP on admission to the ICU was high, at 22.9 ± 2.1 mm Hg. The IAP was significantly lower to 17.2 ± 2.2 mm Hg (p < 0.01) 24 h after the initiation of CVVH, and thereafter decreased rapidly. The average blood level of IL-8 was high at 88.2 ± 25.1 ng/L on admission. However, it significantly decreased to 63.2 ± 18.7 ng/L (p < 0.01) 24 h after the initiation of CVVH, and subsequently decreased. There was a significant positive correlation between the blood level of IL-8 and IAP(r = 0.62, p < 0.01).. CVVH is effective to decrease the IAP and the blood level of IL-8 in ACS patients of SAP. The blood level of IL-8 was significantly correlated with IAP, suggesting that IL-8 might play an important role in the pathogenesis of ACS. Early CVVH appeared to be effective in the treatment of ACS in patients with SAP through the removal of causative cytokines such as IL-8, and it thereby decreased interstitial edema to lower IAP and should be applied in the early stage of ACS. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=480223.

Topics: Female; Hemofiltration; Humans; Interleukin-8; Intra-Abdominal Hypertension; Male; Pancreatitis; Pressure; Severity of Illness Index

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

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

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

Glutamine, a conditionally essential amino acid, is important for immune function. It is now being formulated for incorporation into total parenteral nutrition (TPN). The aims of this study were to examine the effect of glutamine administration on lymphocyte proliferation and proinflammatory cytokine release in patients with severe acute pancreatitis. Fourteen patients were randomized (in a double-blind fashion) to receive either conventional or isocaloric, isonitrogenous glutamine-supplemented (0.22 g glutamine x kg(-1) x d(-1) as glycyl-glutamine) TPN for 7 d. DNA synthesis (index of lymphocyte proliferation) and the 24-h release of tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 from peripheral blood mononuclear cells were measured in vitro on days 0, 4, and 7. Thirteen patients completed the study protocol (6 glutamine TPN, 7 conventional TPN). Glutamine supplementation increased median DNA synthesis by 3099 cpm over the study period against 219 cpm in the conventional group (increase not significantly different between the two groups) . Glutamine supplementation did not significantly influence TNF or IL-6 release, but, in contrast, median IL-8 release was reduced by day 7 in the glutamine group while it was increased in the conventional group (-17.7 ng/mL (median change over study period) versus +43.3 ng/mL, respectively; P=0.045). Small patient numbers and substantial interindividual variation limit the conclusions, but there is a trend for the glutamine group to have improved lymphocyte proliferation, and in the case of IL-8, reduced proinflammatory cytokine release.

Topics: Adult; DNA; Double-Blind Method; Female; Glutamine; Humans; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Pancreatitis; Parenteral Nutrition, Total; T-Lymphocytes

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

Acute pancreatitis is one of the leading causes of gastrointestinal disorder-related hospitalizations, yet its pathogenesis remains to be fully elucidated. Postsynaptic density protein-95 (PSD-95) is closely associated with tissue inflammation and injury. We aimed to investigate the expression of PSD-95 in pancreatic acinar cells, and its function in regulating the inflammatory response and pancreatic pathological damage in acute pancreatitis. A mouse model of edematous acute pancreatitis was induced with caerulein and lipopolysaccharide in C57BL/6 mice. Tat-N-dimer was injected to inhibit the PSD-95 activity separately, or simultaneously with SB203580, inhibitor of p38 MAPK phosphorylation. Rat pancreatic acinar cells AR42J were cultured with 1 μM caerulein to build a cell model of acute pancreatitis. PSD-95-knockdown and negative control cell lines were constructed by lentiviral transfection of AR42J cells. Paraffin-embedded pancreatic tissue samples were processed for routine HE staining to evaluate the pathological changes of human and mouse pancreatic tissues. Serum amylase and inflammatory cytokine levels were detected with specific ELISA kits. Immunofluorescence, immunohistochemical, Western-blot, and qRT-PCR were used to detect the expression levels of PSD-95, p38, and phosphorylated p38. Our findings showed that PSD-95 is expressed in the pancreatic tissues of humans, C57BL/6 mice, and AR42J cells, primarily in the cytoplasm. PSD-95 expression increased at 2 h, reaching the peak at 6 h in mice and 12 h in AR42J cells. IL-6, IL-8, and TNF-α increased within 2 h of disease induction. The pancreatic histopathologic score was greater in the PSD-95 inhibition group compared with the control (

Topics: Acinar Cells; Animals; Cell Line; Disks Large Homolog 4 Protein; Imidazoles; Interleukin-6; Interleukin-8; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; p38 Mitogen-Activated Protein Kinases; Pancreas; Pancreatitis; Protein Kinase Inhibitors; Pyridines; Rats; Tumor Necrosis Factor-alpha

To study the natural course of patients with acute pancreatitis (AP) with acute kidney injury (AKI) and their cytokine profile.. Natural course of patients with AP and AKI was studied in 97 individuals. Levels of TNFα, IL-6, IL-10, IL-8 and IL-1β were measured at presentation and at 72 h in patients who developed AKI.. Amongst the entire cohort, 16.4% patients developed AKI (persistent AKI - 11 patients, transient AKI - 5 patients). Mortality rate was 25% amongst patients with AKI. Levels of IL-6 (p = 0.035) and IL-8 (p = 0.002) were found to be significantly higher in the AKI group. On multivariate analysis, IL-8 levels at baseline were found to be an independent predictor of AKI. AKI group had significant rise of TNF-α (P < 0.001), IL-6 (P < 0.001) and IL- 1β (P < 0.001) on day 3 whereas persistent-AKI group had significant rise of TNF-α (p = 0.031), IL-6 (p = 0.001) and IL-1β on day 3 and significant decline of IL-10 (p = 0.015). Using a cut-off of 105 pg/ml, IL-8 levels at baseline could predict AKI with a sensitivity of 87.5% and specificity of 59.2%, with area under the curve being 0.744 (p = 0.002).. AP patients developing AKI have poor prognosis. IL-8 levels can predict AKI in patients with AP.

Topics: Acute Kidney Injury; Adult; Cytokines; Female; Humans; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Pancreatitis; Prospective Studies; Tumor Necrosis Factor-alpha

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

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

Longer pre-centrifugation times alter the quality of serum and plasma samples. Markers for such delays in sample processing and hence for the sample quality, have been identified.. Twenty cytokines in serum, EDTA plasma and citrate plasma samples were screened for changes in concentration induced by extended blood pre-centrifugation delays at room temperature. The two cytokines that showed the largest changes were further validated for their "diagnostic performance" in identifying serum or plasma samples with extended pre-centrifugation times.. In this study, using R&D Systems ELISA kits, EDTA plasma samples and serum samples with a pre-centrifugation delay longer than 24 h had an IL16 concentration higher than 313 pg/mL, and an IL8 concentration higher than 125 pg/mL, respectively. EDTA plasma samples with a pre-centrifugation delay longer than 48 h had an IL16 concentration higher than 897 pg/mL, citrate plasma samples had an IL8 concentration higher than 21.5 pg/mL and serum samples had an IL8 concentration higher than 528 pg/mL.. These robust and accurate tools, based on simple and commercially available ELISA assays can greatly facilitate qualification of serum and plasma legacy collections with undocumented pre-analytics.

Topics: Adult; Arthritis, Rheumatoid; Biomarkers; Blood Chemical Analysis; Centrifugation; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-16; Interleukin-8; Male; Middle Aged; Pancreatitis; ROC Curve; Specimen Handling; Temperature; Time Factors; Young Adult

Chemokine CCL14 is inactive in its proform. Here, we show that inflammation- and cancer-associated kallikrein-related peptidases KLK5 and KLK8 remove the N-terminal eight amino acids from the proform thereby converting CCL14 to its active state. Activity of the chemokine is demonstrated by migration of myeloid cells expressing relevant receptors.

Topics: Asthma; Atherosclerosis; Cell Line, Tumor; Chemokine CX3CL1; Chemokine CXCL12; Chemokines; Chemokines, CC; Crohn Disease; Enzyme Activation; Humans; Interleukin-8; Kallikreins; Leukemia; Macrophage Inflammatory Proteins; Pancreatitis; Reactive Oxygen Species

BACKGROUND The aim of this study was to explore the risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and investigate the effect of octreotide combined with nonsteroidal anti-inflammatory drugs on preventing its occurrence. MATERIAL AND METHODS A total of 139 patients undergoing ERCP in our hospital from May 2016 to April 2017 were retrospectively analyzed, and divided into an observation group (n=67) (octreotide + indomethacin) and a control group (n=72) (no preventive drugs). The preoperative and postoperative inflammatory cytokines such as tumor necrosis factor-α (TNF)-α, interleukin-6 (IL-6) and IL-8, and serum amylase levels were measured, and the incidence of pancreatitis and hyper amylasemia were monitored. RESULTS Serum amylase level was increased significantly 3 hours after operation in both groups with significantly higher level in the control group compared to the observation group. After 24 hours, serum amylase in the observation group was decreased to preoperative level, whereas it was still higher than preoperative in the control group (P<0.05). Regarding the levels of TNF-α, IL-6, IL-8, and visual analogue scale, they were significantly increased in both groups after operation with significantly higher levels in the control group compared to the observation group (P<0.05). Furthermore, logistic regression analysis showed that difficult intubation, pancreatic duct angiography, surgery for a long time, and the history of previous pancreatitis were risk factors for post-ERCP pancreatitis (P<0.05). CONCLUSIONS Difficult intubation, pancreatic duct angiography, surgery for a long time, and the history of previous pancreatitis were risk factors for post-ERCP pancreatitis. Octreotide combined with non-steroidal anti-inflammatory drugs can reduce the pain of patients with abdominal pain as well as the incidence of postoperative pancreatitis, indicating that they might be effective preventative approaches for pancreatitis.

Topics: Abdominal Pain; Adult; Aged; Amylases; Anti-Inflammatory Agents, Non-Steroidal; China; Cholangiopancreatography, Endoscopic Retrograde; Drug Therapy, Combination; Female; Humans; Indomethacin; Interleukin-6; Interleukin-8; Male; Middle Aged; Octreotide; Pancreatitis; Retrospective Studies; Risk Factors; Tumor Necrosis Factor-alpha

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

Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (P<0.001). In immunostaining, IL-8 expression was detected in the ductal/ductular epithelium (11/13; 85%) and infiltrating neutrophils or lymphocytes (12/12; 100%) in type 2 AIP, but was almost entirely negative in type 1 AIP (n=13; both, P<0.001). Although obstructive pancreatitis adjacent to pancreatic cancers (peritumoral pancreatitis) exhibited IL-8 expression in the epithelium (3/12; 25%) and inflammatory cells (10/12; 83%), expression levels were significantly lower than those in type 2 AIP (P<0.001 and 0.020, respectively). The presence of either GELs or IL-8-positive epithelium discriminated type 2 AIP from type 1 AIP or obstructive pancreatitis with 92% sensitivity and 92% to 100% specificity. Furthermore, CD3/IL-8-coexpressing lymphocytes were almost restricted to type 2 AIP. Interestingly, a similar pattern of IL-8 expression was also observed in colonic biopsies of ulcerative colitis. In conclusion, the overexpression of IL-8 may underlie the development of GELs in type 2 AIP, and IL-8 immunostaining or IL-8/CD3 double staining may become an ancillary method for its diagnosis. The similar expression pattern of IL-8 in ulcerative colitis also suggests a pathogenetic link between the 2 conditions.

Topics: Adolescent; Adult; Autoimmune Diseases; Colitis, Ulcerative; Female; Granulocytes; Humans; Interleukin-8; Male; Middle Aged; Pancreatitis; Young Adult

Angiotensin-converting enzyme 2 (ACE2), its product angiotensin-(1-7), and its receptor Mas have been shown to moderate the adverse effects of the ACE-angiotensin II-AT1 axis in many diseases. The aim of this study was to determine whether the ACE2-Ang-(1-7)-Mas axis could have similar effects in a cell culture model of pancreatic damage.. AR42J cells were stimulated with 10 nmol/L cerulein to simulate acute pancreatitis. ACE2, Ang-(1-7), Mas receptor, and PI3K/AKT pathway were measured by quantitative real-time polymerase chain reaction and Western blot analysis.. ACE2 and Mas receptor protein levels in AR42J cells were significantly increased (P < 0.05) between 30 minutes and 6 hours postdisease induction compared with the control group. Mas receptor gene expression was significantly increased (P < 0.05) at 2 hours postdisease induction, and Ang-(1-7) was increased at 6 hours. Treatment with Ang-(1-7) in AR42J cells increased IL-10, decreased IL-6 and IL-8, and reduced the damage to pancreatic cells. Levels of IL-6 and IL-8 in AR42J cell culture were increased significantly after treatment with A779. Moreover, Ang-(1-7) increased the concentration of PI3K/AKT pathway and eNOSin AR42J cells.. ACE2-angiotensin-(1-7)-Mas axis significantly inhibits pancreatitis in response to decreased inflammatory factors by the activation of endothelial nitric oxide synthase and NO signaling pathways.

Topics: Angiotensin I; Angiotensin-Converting Enzyme 2; Animals; Anti-Inflammatory Agents; Cell Line; Ceruletide; Cytoprotection; Inflammation Mediators; Interleukin-6; Interleukin-8; Nitric Oxide; Nitric Oxide Synthase Type III; Pancreas, Exocrine; Pancreatitis; Peptide Fragments; Peptidyl-Dipeptidase A; Phosphatidylinositol 3-Kinase; Phosphorylation; Proto-Oncogene Mas; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Rats; Receptors, G-Protein-Coupled; 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

The investigation was performed in 47 patients, operated on for pancreatic pseudocysts (PP). The PP type was established in accordance to A. D'Egidio, M. Schein (1991) classification. The blood plasma contents of proinflammatory and antiinflammatory cytokines, including interleukins (IL): IL-6, IL-8, IL-10, IL-18, as well as malonic dialdehyde and activity of glutationperoxidase, were determined for estimation of the immune state disorders. Mostly expressed changes in IL-8 content were registered in complicated PP in 72 h postoperatively, what was have characterized by more expressed raising of its level in systemic blood flow, than in a splanchnic one, in all types of PP and witnessed a hepatic capacity to guarantee a cytokine's clearance in all the patients. The contents of glutationperoxidase and IL-18 in the blood serum in various types of PP have correlated immediately with pancreatitis severity. Close correlative connection between these indices while unfavorable prognosis of postoperative period course was established.

Topics: Adult; Biomarkers; Female; Glutathione Peroxidase; Humans; Interleukin-10; Interleukin-18; Interleukin-6; Interleukin-8; Male; Malondialdehyde; Middle Aged; Pancreatic Pseudocyst; Pancreatitis; Prognosis; Severity of Illness Index; Treatment Outcome

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 research aims to investigate the IL-8 А-251Т (rs 4073) gene polymorphism in patients with acute pancreatitis. The frequency of allelic variants of cytokine gene in 100 patients was determined. Genotype А/Т was found in 47.0% of cases (47 patients) of acute pancreatitis, T/T alleles - in 37% of cases (37 patients), A/A alleles in 16% of cases (16 patients). In 73.3% of non-operated patients with destructive forms of acute pancreatitis the reliable (р<0,05) increase of heterozygous carriers of genotype А/Т were detected. In patients with edematous form of acute pancreatitis frequency of А/Т was detected in 42.2% of cases, In control group frequency of А/Т was detected in 46% of cases, The possible association between genotype А/Т and the destruction of the pancreas was determined.

Topics: Alleles; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Interleukin-8; Male; Pancreatitis; Polymorphism, Single Nucleotide

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

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

Biomarkers, such as C-reactive protein [CRP] and procalcitonin [PCT], are insufficiently sensitive or specific to stratify patients with sepsis. We investigate the prognostic value of pancreatic stone protein/regenerating protein (PSP/reg) concentration in patients with severe infections.. PSP/reg, CRP, PCT, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL1-β), IL-6 and IL-8 were prospectively measured in cohort of patients ≥ 18 years of age with severe sepsis or septic shock within 24 hours of admission in a medico-surgical intensive care unit (ICU) of a community and referral university hospital, and the ability to predict in-hospital mortality was determined.. We evaluated 107 patients, 33 with severe sepsis and 74 with septic shock, with in-hospital mortality rates of 6% (2/33) and 25% (17/74), respectively. Plasma concentrations of PSP/reg (343.5 vs. 73.5 ng/ml, P < 0.001), PCT (39.3 vs. 12.0 ng/ml, P < 0.001), IL-8 (682 vs. 184 ng/ml, P < 0.001) and IL-6 (1955 vs. 544 pg/ml, P < 0.01) were significantly higher in patients with septic shock than with severe sepsis. Of note, median PSP/reg was 13.0 ng/ml (IQR: 4.8) in 20 severely burned patients without infection. The area under the ROC curve for PSP/reg (0.65 [95% CI: 0.51 to 0.80]) was higher than for CRP (0.44 [0.29 to 0.60]), PCT 0.46 [0.29 to 0.61]), IL-8 (0.61 [0.43 to 0.77]) or IL-6 (0.59 [0.44 to 0.75]) in predicting in-hospital mortality. In patients with septic shock, PSP/reg was the only biomarker associated with in-hospital mortality (P = 0.049). Risk of mortality increased continuously for each ascending quartile of PSP/reg.. Measurement of PSP/reg concentration within 24 hours of ICU admission may predict in-hospital mortality in patients with septic shock, identifying patients who may benefit most from tailored ICU management.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Health Status Indicators; Hospital Mortality; Humans; Intensive Care Units; Interleukin-1beta; Interleukin-6; Interleukin-8; Lithostathine; Male; Middle Aged; Pancreatitis; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic; 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

To study secretion patterns of pro- and anti-inflammatory cytokines, and activation of various cellular subsets of leukocytes in peripheral blood.. We have conducted a prospective observational study. One hundred and eight patients with a diagnosis of acute pancreatitis and onset of the disease within last 72 h were included in this study. The mRNA expression of 25 different types of cytokines in white blood cells was determined by quantitative real time polymerase chain reaction. Levels of 8 different cytokines in blood serum were measured by enzyme linked immunosorbent assay. Clinical data and cytokine expression results were subjected to statistical analysis.. Severe and necrotizing acute pancreatitis (AP) is characterized by the significant depletion of circulating lymphocytes. Severe acute pancreatitis is associated with a typical systemic inflammatory response syndrome and over-expression of pro-inflammatory cytokines [interleukin (IL)-6, IL-8, macrophage migration inhibitory factor (MIF)]. Serum IL-6 and MIF concentrations are the best discriminators of severe and necrotizing AP as well as possible fatal outcome during the early course of the disease.. Deregulation of cellular immune system is a key event leading to severe and necrotizing AP. IL-6 and MIF could be used as early predictors of complications.

Topics: Adult; Aged; Cytokines; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Immune System; Interleukin-6; Interleukin-8; Leukocytes; Male; Middle Aged; Models, Biological; Pancreatitis; Prognosis; Prospective Studies; RNA, Messenger

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

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

If differences of inflammatory pathways in acute pancreatitis exist for various etiologies, selective and specific antiinflammatory and other modulatory treatment regimens might be indicated. Circulating levels of prominent proinflammatory cytokines IL-6, 8, 18, and TNF-alpha were measured in patients having their first attack of either alcohol- or gallstone-induced acute pancreatitis.. Seventy-five consecutive patients were prospectively included over a 15-month period, sixty of them being either alcohol- or gallstone-induced. All patients were treated according to a standardized algorithm. Blood samples were obtained immediately on admission and, again, at days 1, 2, and 14.. A significant effect of the etiology on the levels of IL-8 in the alcohol group as compared to the gallstone group (P=0.003) was found. No etiologic differences were observed for IL-6, IL-18, TNF-alpha, or CRP. Furthermore, no significant differences, either regarding the need for treatment at the intensive care unit or of 30-day mortality, were found.. The present study confirms previous findings and supports the hypothesis that, except for IL-8, the biochemical profile and clinical outcome is independent of the underlying etiology. Revealing the complex spatial and temporal profile of proinflammatory cytokine expression in acute pancreatitis is necessary and important for the development of a more targeted rational therapy.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Cytokines; Female; Gallstones; Humans; Interleukin-18; Interleukin-6; Interleukin-8; Male; Middle Aged; Pancreatitis; Pancreatitis, Alcoholic; Prospective Studies; Severity of Illness Index; Tumor Necrosis Factor-alpha; Young Adult

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

To study the role of the polymorphonuclear neutrophil (PMN) apoptosis and expression of Fas and caspase-3 in the systemic inflammatory response syndrome (SIRS).. Eight acute pancreatitis patients with SIRS, 6 healthy control subjects were enrolled to study apoptosis of PMN in peripheral blood samples, expression of Fas/Fas ligand (FasL) and caspase-3 in the PMN, the levels of serum interleukin-6 (IL-6) and IL-8 were observed.. Spontaneous apoptosis was significantly delayed in PMN from the SIRS patients with higher serum IL-6 and IL-8 levels compared with controls (both P<0.01). PMN apoptosis rate in peripheral blood of patients with SIRS was lowered than that of controls (P<0.01). The expressions of Fas and caspase-3 in the peripheral circulating PMN were higher in the controls than those in the SIRS patients (both P<0.01). Serum FasL expression was not found by Western blotting 24 hours after culture of PMN in vitro.. Peripheral circulating PMN from acute pancreatitis patients with SIRS show delayed apoptosis, decreased expressions of Fas and caspase-3, and prolonged PMN survival may contribute to the development of systemic inflammatory injury characteristic of SIRS.

Topics: Apoptosis; Caspase 3; Fas Ligand Protein; fas Receptor; Humans; Interleukin-6; Interleukin-8; Neutrophils; Pancreatitis; Systemic Inflammatory Response Syndrome

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

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

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

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

Proinflammatory cytokines play a fundamental role in the local and systemic inflammatory responses in the initial stages of acute biliary pancreatitis (ABP) and in the development of severe forms of the disease.. The aim of the present study was to assess the systemic release of proinflammatory cytokines and to characterize differences between patients with mild ABP (MABP) and severe ABP (SABP).. In the current study, 54 patients with MABP were compared with 14 patients with SABP. Serum levels of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8 and IL-12p40 were measured every second day after admission for one week.. The tumour necrosis factor-alpha level was similar in all days of analysis in patients with MABP but was lower compared with SABP patients. The level of IL-1beta was higher at admission in patients with MABP. The level of IL-6 peaked on admission day in both groups, but in patients with SABP, the obtained values were higher. The level of IL-8 on admission day was slightly higher in patients with MABP and systematically decreased when measured on the following days (the third, fifth and seventh days of the study). An increased level of IL-8 during the third, fifth and seventh days of the investigation was seen in SABP patients. The level of IL-12p40 was slightly higher in patients with MABP on the day of admission.. The levels of some proinflammatory cytokines are higher in patients with SABP than in patients with MABP. The most consistent difference between the two groups was that the levels of IL-6 were significantly higher in patients with SABP throughout the study. Serum concentration of IL-6 may be helpful as a marker of severity and outcome of ABP.

Topics: Adult; Aged, 80 and over; Cytokines; Female; Humans; Interleukin-12 Subunit p40; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Pancreatitis; Severity of Illness Index; 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

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

To evaluate the role of some pro- and anti-inflammatory cytokines, acute phase proteins and biliary-pancreatic reflux in pathogenesis of development and recurrence of chronic recurrent pancreatitis (CRP) and alcohol chronic pancreatitis (ACP).. IL-8, IL-4, IL-10, TNF-alpha, lactoferrin (LF) and cerruloplasmin were estimated by a standard enzyme immunoassay in 186 CRP and 32 ACP patients.. The levels of proinflammatory cytokines, TNF-alpha and IL-8 as well as anti-inflammatory cytokines IL-4 and IL-10 in CRP patients reached their maximum on exacerbation day 5-7 while in ACP--on day 1-2. High cytokines levels correlate with exacerbation severity. In transition to remission, the levels of cytokines and acute phase proteins (lactoferrin, ceruloplasmin) went down. In remission some patients showed episodes of rising IL-8 and TNF-alpha to the level typical for exacerbation but without clinical manifestations. This may point to latent recurrences. TNF-alpha rose in remission most frequently in patients with biliary-pancreatic reflux. Antiinflammatory treatment of duodenitis (papillitis) lowered basal pressure of Oddi's sphincter stopping biliary-pancreatic regurgitation and leading to breaking the pathogenetic chain of CRP exacerbations.. Proinflammatory cytokines TNF-alpha and IL-8 promote development of CRP. This should be taken into consideration while planning combined therapy.

Topics: Bile; Biomarkers; Chronic Disease; Cytokines; Female; Humans; Immunoenzyme Techniques; Interleukin-8; Male; Pancreatic Juice; Pancreatitis; Pancreatitis, Alcoholic; Recurrence; Tumor Necrosis Factor-alpha; Ultrasonography

Obstructive pancreatitis is a specific form of pancreatitis, which is caused by the obstruction of the main pancreatic duct due to tumors or some other causes. Interleukin-8 is induced in acute pancreatitis, but its expression in obstructive pancreatitis has not been clarified.. We attempted to provide some insight into the significance of interleukin -8 in the pathogenesis of pancreatic fibrosis.. Fifteen cases of pancreatic cancer, 7 cases of mucinous cystadenoma, 3 cases of Vater's papilla cancer and 9 normal pancreases were included in this study.. The obstructive pancreatitis portions of the above pathologies were evaluated for interleukin-8 expression by means of immunohistochemistry and in situ hybridization.. Interleukin-8 was positive in 72% of cases of obstructive pancreatitis. The positive rate was not significantly related to the etiology of the obstruction (P=0.972). Interleukin-8 was expressed in infiltrating cells, proliferating ductular cells and acinar cells. In contrast, normal pancreases and tumor cells lacked interleukin-8 expression (P<0.001 vs. obstructive pancreatitis). Both immunohistochemistry and in situ hybridization demonstrated that interleukin-8 was expressed mostly in acinar cells in mild pancreatic fibrosis, whereas it was expressed in stromal and ductular cells in moderate and severe pancreatic fibrosis.. These results suggest that interleukin-8 expression is related to the fibrotic process in obstructive pancreatitis.

Topics: Aged; Carcinoma, Islet Cell; Carcinoma, Pancreatic Ductal; Cystadenoma, Mucinous; Cytoplasm; Female; Humans; Immunohistochemistry; Interleukin-8; Male; Middle Aged; Pancreatic Neoplasms; Pancreatitis; RNA, Messenger; RNA, Neoplasm; Stromal Cells

Pancreatic cancer is the most deadly of all gastrointestinal (GI) malignancies, yet relatively little is known regarding mechanisms of tumor development including the role of inflammation.. Chronic pancreatitis (CP) increases the risk of developing cancer by 10- to 20-fold; mediators of the chronic inflammatory process and the surrounding fibrotic stroma likely support a transformation to malignancy, yet the exact mechanisms remain undefined. The purpose of our present study was to determine potential inflammatory components in epithelial and stromal cells that may contribute to both CP and pancreatic cancers.. Specimens of normal pancreas, CP, and pancreatic cancer were examined using laser-capture microdissection (LCM), gene array, and immunohistochemistry.. Gene array analysis from LCM-dissected tissues demonstrated: (i) increased expression of interleukin-8 (IL-8), an activator of the inflammatory factor nuclear factor-kappaB (NF-kappaB), and (ii) decreased expression of IkappaB (an inhibitor of NF-kappaB) in CP ductal cells compared with normal ducts. Compared with CP, cancers demonstrated: (i) increased expression of tumor related genes including S100A4, cyclin E1, and epidermal growth factor (EGF) receptor, and (ii) expression of matrix metalloproteinase 2, a pro-invasive factor for tumor cells, which was not present in the CP stroma. Increased staining of both the p50 NF-kappaB subunit and IKKalpha kinase (a protein that allows activation of NF-kappaB) was noted in CP and cancers.. Our results demonstrate that similar inflammatory components and downstream effectors are present in CP and pancreatic cancers. Importantly, these findings suggest that a common pathway for pancreatic cancer development may be through a chronic inflammatory process including stroma formation. These findings may lead to novel strategies for pancreatic cancer prophylaxis based on inhibition of inflammatory mediators.

Topics: Biomarkers, Tumor; Case-Control Studies; Cell Transformation, Neoplastic; Cells, Cultured; Chronic Disease; Culture Techniques; Female; Humans; Immunohistochemistry; Inflammation Mediators; Interleukin-8; Male; NF-kappa B; Pancreatic Ducts; Pancreatic Neoplasms; Pancreatitis; Precancerous Conditions; Prognosis; Sensitivity and Specificity

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

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

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

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

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

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

To test the hypothesis that elevated concentrations of interleukin-8 associated with anti-interleukin-8 autoantibodies (anti-interleukin-8:interleukin-8 complexes) are found in patients at risk for acute respiratory distress syndrome who developed the disease.. Measurement of anti-interleukin-8:interleukin-8 complex concentrations in previously collected bronchoalveolar lavage fluids. These fluids were obtained from patients at risk for acute respiratory distress syndrome who subsequently either recovered or developed acute respiratory distress syndrome.. A unique population of patients at risk for acute respiratory distress syndrome was studied. There were 26 patients at risk for acute respiratory distress syndrome who were divided into three groups. Group I patients had high interleukin-8 concentrations and developed acute respiratory distress syndrome, group II had high interleukin-8 concentrations and did not develop acute respiratory distress syndrome, and group III had low interleukin-8 concentrations and did not develop acute respiratory distress syndrome. These patients were selected to test the hypothesis that presence of elevated concentrations of anti-interleukin-8:interleukin-8 complexes differentiates patients at risk for acute respiratory distress syndrome who developed acute respiratory distress syndrome from patients who did not.. Bronchoalveolar lavage fluid concentrations of interleukin-8 associated with the anti-interleukin-8 autoantibodies were significantly different between groups (p <.03). The amount of interleukin-8 bound to the anti-interleukin-8 autoantibody was higher in group I than in group II and group III.. Bronchoalveolar lavage fluid concentration of anti-interleukin-8:interleukin-8 complexes may serve as a marker of disease progression in patients at risk for acute respiratory distress syndrome.

Topics: Antigen-Antibody Complex; Autoantibodies; Biomarkers; Bronchoalveolar Lavage Fluid; Humans; Interleukin-8; Intestinal Perforation; Multiple Trauma; Pancreatitis; Respiratory Distress Syndrome; Risk Factors

This study aimed to analyze the therapeutic effects of the carboxamide derivative IS-741 on spontaneous chronic pancreatitis (CP) in the WBN/Kob rat. Four-week-old male WBN/Kob rats were fed with MB-3, and IS-741 (0.012% in MB-3) was orally administered for 12 weeks. Cytokine-induced neutrophil chemoattractant (CINC), interleukin (IL) -6, pancreatitis-associated protein (PAP), and p8 mRNAs in the pancreas were detected with semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Histological examination of the pancreas showed that hemorrhage, interstitial edema, and inflammatory cell infiltration were markedly less severe at 12 weeks, while fibrosis and acinar degeneration were also milder at 16 weeks, in the IS-741-treated rats than in untreated rats. The above-mentioned genes were significantly suppressed in IS-741-treated rats at 12 weeks. Our results show that IS-741 exerts a potentially therapeutic effect on experimental CP by suppressing the expressions of the proinflammatory cytokines (IL-6 and CINC) and pancreatic acute phase proteins (PAP and p8).

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Chronic Disease; Immunohistochemistry; Interleukin-6; Interleukin-8; Male; Pancreatitis; Pancreatitis-Associated Proteins; Polymerase Chain Reaction; Propiophenones; Pyridines; Rats

Thiazolidinedione derivatives are known to be novel insulin-sensitizing agents and ligands of a nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma). Recently, ligands of PPARgamma have been shown to modulate proinflammatory cytokine production and NF-kappaB activation.. To show that thiazolidinedione derivatives interfere with the development of chronic pancreatitis.. Rat chow containing 0.2% troglitazone was administered from 1 month to 7 months of age in WBN/Kob rats with spontaneous chronic pancreatitis. Morphologic evaluation of the pancreas was performed at 4 months and 7 months of age. Pancreas weight, protein, amylase, and insulin contents also were determined. Changes of cytokine levels were detected by enzyme-linked immunosorbent assay or semiquantitative reverse transcription-polymerase chain reaction. Localization and expression of PPARgamma in the pancreas and isolated peritoneal macrophages were examined by immunohistochemical study.. Administration of troglitazone reduced the severity of morphologic pancreatic damage including inflammatory cell infiltration, and fibrosis markedly improved by the administration of troglitazone. Further, troglitazone was able to prevent the decrease in amylase content and pancreas atrophy that were observed in WBN/Kob rats. Serum IL-8 levels and TNF-alpha mRNA levels in the pancreas were significantly elevated in WBN/Kob rats, and these were dramatically attenuated by troglitazone. Peritoneal macrophages isolated from normal rats expressed PPARgamma at low levels, whereas those from WBN/Kob rat abundantly expressed PPARgamma.. Troglitazone prevented the progression of pancreatic inflammatory process in an animal model of chronic pancreatitis. Macrophages may be one of the targets of the PPARgamma ligand to attenuate the severity of chronic pancreatitis, partially mediated by the inhibition of proinflammatory cytokine gene expression.

Topics: Amylases; Animals; Antineoplastic Agents; Blood Glucose; Chromans; Chronic Disease; Disease Models, Animal; DNA; Gene Expression; Hypoglycemic Agents; Insulin; Interleukin-8; Macrophages, Peritoneal; Male; Organ Size; Pancreatitis; Rats; Rats, Wistar; Receptors, Cytoplasmic and Nuclear; Thiazoles; Thiazolidinediones; Transcription Factors; Troglitazone; Tumor Necrosis Factor-alpha

The pathogenesis of chronic pancreatitis (CP), especially of acinar cell injury, is still unclear. Interleukin (IL)-8 is a chemokine that is involved in various inflammatory diseases.. To examine whether IL-8 and other chemokines are expressed in experimental acinar cell injury.. IL-8 expression was analyzed in spontaneous CP in the WBN/Kob rat and in rat pancreatic acinar AR4-2J cells treated with various stimuli using reverse transcription-polymerase chain reaction (semiquantitative) and immunohistochemistry.. Chronic pancreatitis developed at 12 weeks in the WBN/Kob rats. IL-8, macrophage chemoattractant protein-1, and macrophage inflammatory protein-2 mRNA was expressed from 4 weeks and peaked at 12 weeks. Immunohistochemistry showed a strong expression of IL-8 in acinar cells, proliferating ductular cells, and interstitial infiltrating cells. In contrast, normal pancreatic tissues lacked IL-8 expression. Further, IL-8 mRNA and protein were detectable in AR4-2J cells treated with the various stimuli, such as menadione, tumor necrosis factor-alpha and transforming growth factor beta1.. These results suggest that IL-8 is expressed in the pancreatic parenchyma and infiltrates in CP and that it plays a role in the initial pathogenesis of CP together with other chemokines and cytokines.

Topics: Animals; Cells, Cultured; Chemokine CCL2; Chemokine CXCL2; Chemokines; Chronic Disease; Disease Models, Animal; Gene Expression; In Vitro Techniques; Interleukin-8; Male; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Pancreas; Pancreatitis; Rats; Rats, Wistar

In a recent study we have demonstrated that interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) serum levels correlate positively with the severity of acute pancreatitis (AP), induced by bile acid injected into the pancreatic duct of rabbits. In this article we describe the effect of an IL-10 analogue IT9302 and a monoclonal anti-IL-8 (mon. IL-8) antibody on the content of several pro-inflammatory cytokines in the serum of rabbits, after induction of AP. We found that the serum content of inflammatory cytokines IL-8, IL-1beta, TNF-alpha and monocyte chemoattractant protein 1 (MCP-1) are increased during AP. Injection of IT9302 or mon. IL-8 antibody, diminish the concentration of these cytokines in the serum, with the exception that mon. IL-8 antibody actually increased the circulating level of MCP-1. In addition, intravenous administration of IT9302 increased the serum levels of IRAP, an IL-1beta receptor antagonistic cytokine. Furthermore, intravenous injection of mon. IL-8 antibody increased serum levels of IL-4. It can be concluded that both the human IL-10 analogue IT9302 and mon. IL-8 antibody are able to alter the pro-inflammatory cytokine levels in rabbits suffering from experimentally induced AP.

Topics: Animals; Antibodies, Monoclonal; Bile Acids and Salts; Chemokine CCL2; Cytokines; Dose-Response Relationship, Drug; Female; Humans; Interleukin-1; Interleukin-8; Male; Oligopeptides; Pancreatitis; Peroxidase; Rabbits; Time Factors; Tumor Necrosis Factor-alpha

Systemic inflammation triggered by insults like sepsis and acute pancreatitis may play a role in development of indirect acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Because little is known about the course of systemic inflammation on the days preceding diagnosis of ARDS, we prospectively monitored immune inflammatory status in 52 patients at risk and we assessed the presence of ALI and ARDS on day 7 after admission to the intensive care unit. On admission, serum interleukin (IL) 8, IL-6, and soluble IL-2 receptor concentrations were significantly higher in patients with subsequent ALI (n = 18) than in patients without ALI (n = 30). During a 4-day follow-up, IL-8 and IL-6 levels of ALI patients remained high and those of non-ALI patients decreased. None of the markers discriminated ARDS patients (n = 9) from non-ARDS ALI patients (n = 9). Among 11 patients with acute pancreatitis, ALI patients had significantly higher IL-8, IL-6, and phagocyte CD11b expression levels than did non-ALI patients, whereas among 14 patients with massive transfusion, respective findings in ALI and non-ALI patients were comparable. Results give credence to the view that systemic inflammation plays a role in development of ALI triggered by pancreatitis, but not in that by massive transfusion. This finding, if confirmed in studies with sufficient statistical power, suggests that the patients with massive transfusion do not necessarily benefit from novel biotherapies aimed at altering the course of systemic inflammation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Critical Care; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Lung Injury; Male; Middle Aged; Pancreatitis; Prospective Studies; Receptors, Interleukin-2; Respiratory Distress Syndrome; Transfusion Reaction

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

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

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

Interleukin-8 was examined in 55 patients with chronic relapsing pancreatitis in the stage of aggravation, change to remission and stable remission. The highest interleukin-8 was revealed in the patients with aggravation of pancreatitis. The author considers, that interleukin-8 is connected with high concentration of oxygen active forms in neutrophils in the patients with this stage of disease. It is concluded, that interleukin-8 takes part in the pathogenesis of relapsing pancreatitis. High levels of interleukin-8 were revealed in some patients with stable pancreatitis remission. The author thinks, that asymptomatic pancreatitis relapses may be present.

Topics: Chronic Disease; Humans; Interleukin-8; Pancreatitis; Recurrence; Severity of Illness Index

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

Cellular infiltrates are present already in early stages of chronic pancreatitis. The mechanisms responsible for their recruitment are unknown. Hence, we determined the differential expression of chemokine genes and their cellular sources in normal and affected pancreatic tissues.. Pancreatic tissues from 23 patients with chronic pancreatitis and from 4 normal controls were subjected to in situ hybridization for detecting messenger RNA (mRNA) of the chemokine genes interleukin 8, ENA-78, MIG, MCP-1, and I-309.. Normal pancreatic tissues lack cells expressing mRNA for IL-8, ENA-78, MIG, and MCP-1. In contrast, pancreatic lobuli with mild to moderate signs of tissue alterations strongly expressed MCP-1 mRNA in centroacinar ducts, endothelia, fibroblasts, macrophages, T cells, and occasionally in nerves. Interleukin 8 and ENA-78 mRNA is preferentially detected in centroacinar ducts of pancreatic lobuli with more advanced alterations. Variable numbers of pancreas-infiltrating T cells express MIG mRNA. I-309 mRNA, however, is consistently observed in normal acini and in tissue with mild to moderate signs of tissue alterations.. The observed differential expression of distinct chemokine genes in pancreatic parenchyma and infiltrates from patients with chronic pancreatitis strongly suggests an involvement of distinct chemokines in the initiation and perpetuation of disease.

Topics: Adult; Chemokine CCL2; Chemokine CXCL5; Chemokine CXCL9; Chemokines; Chemokines, CXC; Chronic Disease; Female; Fibrosis; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-8; Macrophages; Male; Middle Aged; Pancreas; Pancreatic Ducts; Pancreatitis; RNA, Messenger; T-Lymphocytes

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

Changes in substance P content and a relationship between the degree of perineural inflammation and pain has been demonstrated in chronic pancreatitis. Whether a relationship exists between neural alteration and pancreatic inflammation (neurogenic inflammation) is not known.. In the present study we evaluated gene expression of preprotachykinin A (PPT-A), the gene encoding substance P, and interleukin 8, a proinflammatory and hyperalgesic mediator whose release is co-regulated by substance P.. Pancreatic tissue specimens obtained from 21 patients (16 male, five female) with chronic pancreatitis and 18 healthy organ donors (nine male, nine female) were analysed.. Gene expression of PPT-A and interleukin 8 was studied by northern blot analysis. Respective proteins were localised using immunohistochemistry.. Northern blot analysis showed that PTT-A mRNA expression levels were present at comparable levels in normal and chronic pancreatitis tissue samples. In contrast, interleukin 8 mRNA was expressed at very low levels in normal controls but was increased 41-fold (p<0. 001) in chronic pancreatitis tissue samples. Using immunohistochemistry, interleukin 8 protein was localised mainly in immune cells often found around enlarged pancreatic nerves. In addition, in chronic pancreatitis, intense interleukin 8 immunostaining was present in metaplastic ductal cells of the atrophic pancreatic parenchyma. In chronic pancreatitis samples there was a positive relationship between interleukin 8 mRNA levels and the presence of ductal metaplasia (r=0.795; p<0.001) and the inflammation score (r=0.713; p<0.001).. Our data indicate that in chronic pancreatitis, the increase in substance P in enlarged pancreatic nerves is not caused by enhanced intrapancreatic PTT-A mRNA expression, suggesting that the location of substance P synthesis is outside of the pancreas. In addition, localisation of interleukin 8 positive immune cells around pancreatic nerves further supports the existence of neuroimmune interactions as a pathophysiological mechanism in chronic pancreatitis.

Topics: Adult; Blotting, Northern; Case-Control Studies; Chronic Disease; Female; Gene Expression; Humans; Interleukin-8; Male; Middle Aged; Pancreas; Pancreatic Ducts; Pancreatitis; Protein Precursors; RNA, Messenger; Substance P; Tachykinins

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

Although altered cytokine homeostasis has been implicated in the pathogenesis of both alcoholic liver and pancreas diseases, the serum cytokine pattern characteristic of concomitant alcoholic liver cirrhosis and pancreatitis has not been examined. In this paper we examine the serum levels of proinflammatory cytokines, such as IL-6, IL-8, TNF-alpha, and also antiinflammatory ones, such as IL-10 and TGF-beta, in 22 patients with alcoholic liver cirrhosis and 28 patients with chronic pancreatitis and compare them with those detected in the sera of 14 patients with concomitant alcoholic cirrhosis and pancreatitis. All patients were heavy alcohol drinkers, consuming more than 70 g of pure alcohol per day for at least 5 years. The control group consisted of 33 age- and sex-matched healthy subjects receiving an annual health examination. They were not addicted to alcohol and confirmed to be free of major cardiopulmonary, gastrointestinal and hepatobiliary-pancreatic diseases. The results indicated that the cytokine pattern in the sera of patients with concomitant liver cirrhosis and pancreatitis was characterized by increased levels of two proinflammatory cytokines: TNF-alpha, the concentration of which seemed to be influenced by both liver and pancreas injury, and IL-6, which seemed to be rather connected with pancreas injury. Increased levels of IL-8, which were detected in the sera of patients with cirrhosis, pancreatitis and concomitant cirrhosis and pancreatitis, were rather connected with exacerbation of the disease processes which occurred only in some of the patients. No significant changes in the levels of IL-10 or TGF-beta were detected in the sera of patients with chronic pancreatitis and concomitant cirrhosis and pancreatitis, while in patients with cirrhosis significantly decreased levels of IL-10 were found. A significant imbalance between proinflammatory/antiinflammatory signals was especially characteristic of alcoholic cirrhosis and concomitant cirrhosis with pancreatitis.

Topics: Adult; Alcohol Drinking; Cytokines; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Pancreatitis; Tumor Necrosis Factor-alpha

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

The priming mechanism of macrophages to secrete cytokines in acute pancreatitis is important for remote organ failure following septic complication. The effects of novel carboxamide derivative, IS-741, on neutrophil chemoattractant production by bronchoalveolar macrophages were studied in rats with cerulein-induced pancreatitis complicated by sepsis.. Pancreatitis was induced by four intramuscular injections of cerulein (50 microg/kg at 1-hour intervals). Pancreatitis rats were injected intraperitoneally with 10 mg/kg of lipopolysaccharide (LPS) 6 h following the first cerulein injection as a septic challenge. Pancreatitis rats received a continuous intravenous injection of IS-741 (3 mg/kg/h) 30 min before the septic challenge.. Intense mononuclear cell infiltration and lung hemorrhage occurred in untreated pancreatitis rats complicated with sepsis, but hemorrhage was not seen in septic pancreatitis rats receiving a continuous intravenous injection of IS-741 shortly before sepsis induction. The IS-741-treated rats had lower serum concentrations of cytokine-induced neutrophil chemoattractant (CINC), as well as fewer the pulmonary neutrophils and infiltrates immunoreactive for CINC or Mac-1 (CD11b/CD18).. The novel carboxamide derivative IS-741 reduced CINC production by bronchoalveolar macrophages and effectively prevented pancreatitis-associated lung injury following the septic challenge.

Topics: Animals; CD18 Antigens; Ceruletide; Chemotaxis; Disease Models, Animal; Enzyme Inhibitors; Injections, Intravenous; Interleukin-8; Macrophage-1 Antigen; Macrophages, Alveolar; Male; Neutrophil Infiltration; Pancreatitis; Pyridines; Rats; Rats, Wistar; Sepsis

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

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

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

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

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

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

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

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 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

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

Neutrophils have been implicated in the pathogenesis of the adult respiratory distress syndrome (ARDS). We have measured concentrations of the neutrophil attractant interleukin-8 in blood and bronchoalveolar lavage fluid (BAL) from patients at risk of ARDS. We studied 29 patients from three groups at risk of developing ARDS: multiple trauma (n = 16), perforated bowel (n = 6), and pancreatitis (n = 7). ARDS developed in 7 of these patients. Interleukin-8 in BAL and blood samples taken on initial hospital presentation was measured by a sandwich enzyme-linked immunosorbent assay. The mean BAL interleukin-8 concentration was significantly higher for the patients who subsequently progressed to ARDS than for the non-ARDS group (3.06 [SE 2.64] vs 0.053 [0.010] ng/mL, p = 0.0006). There was no difference between the groups in plasma interleukin-8 (6.23 [2.60] vs 5.12 [2.22] ng/mL, p = 0.31). Immunocytochemistry suggested that the alveolar macrophage is an important source of interleukin-8 at this early stage in ARDS development. This study provides evidence of a relation between the presence of interleukin-8 in early BAL samples and the development of ARDS. The early appearance of interleukin-8 in BAL of patients at risk of ARDS may be an important prognostic indicator for the development of the disorder and reinforces the likely importance of neutrophils and the effects of their accumulation and activation in the pathogenesis of many cases of ARDS.

Topics: Adolescent; Adult; Aged; Bronchoalveolar Lavage Fluid; Humans; Interleukin-8; Intestinal Perforation; Middle Aged; Multiple Trauma; Pancreatitis; Prognosis; Respiratory Distress Syndrome; Risk Factors

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