interleukin-8 and Bacteremia

Sepsis, severe sepsis, and septic shock cause significant morbidity and mortality worldwide. Rapid diagnosis and therapeutic interventions are desirable to improve the overall mortality in patients with sepsis. However, gold standard laboratory diagnostic methods for sepsis, pose a significant challenge to rapid diagnosis of sepsis by physicians and laboratories. This article discusses the usefulness and potential of biomarkers and molecular test methods for a more rapid clinical and laboratory diagnosis of sepsis. Because new technologies are quickly emerging, physicians and laboratories must appreciate the key factors and characteristics that affect the clinical usefulness and diagnostic accuracy of these test methodologies.

Topics: Acute-Phase Proteins; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carrier Proteins; Clinical Laboratory Techniques; Humans; Interleukin-6; Interleukin-8; Laboratories; Membrane Glycoproteins; Nucleic Acid Amplification Techniques; Protein Precursors; Sepsis; Serum Amyloid P-Component; Vasopressins

The diagnosis of neonatal bacterial infection remains one of the greatest and most tantalizing challenges to neonatologists. At birth it must be based on the history of pregnancy and take into account a number of now well-defined risk factors. In addition, if promptly started, antibiotic therapy can reduce its sequelae and improve the prognosis. However, the number of tests that obstetricians can rely on for the diagnosis of infection is quite limited. Tests of maternal inflammation indicators have a low specificity, culture tests are not immune from the risk of contamination, and the measurement of interleukins in the amniotic fluid and maternal blood serum is not yet routine. Observation of clinical signs therefore remains crucial to neonatologists, at the same time that new and more sophisticated laboratory tests enable them to establish a diagnosis of infection at an increasingly earlier stage. In recent years, several infection markers have been investigated, such as procalcitonin and especially C-reactive protein (CRP). Currently, the measurement of plasma concentrations of interleukins (IL), IL-6 and IL-8 in particular, appears to be one of the most sensitive and specific infection indicators in newborns. Cytokine levels are increased even before infants develop any clinical symptoms and routine laboratory tests turn positive. However, owing to their short half-life, their sensitivity decreases after 12-24 h from the onset of inflammation, increasing the risk of false negatives. Ideally, they should then be used in combination with other inflammation indicators, such as CRP. The measurement of cytokines and other new inflammatory markers might be helpful in the early diagnosis of both early-onset infection (assay in umbilical cord blood) and late-onset infection (serial assays performed during the stay in the neonatal intensive care unit). In spite of their time-consuming techniques, culture tests remain of the utmost importance to plan a targeted treatment; blood culture, in particular, is crucial to the diagnosis of sepsis.

Topics: Bacteremia; Biomarkers; Humans; Infant, Newborn; Infant, Newborn, Diseases; Interleukin-6; Interleukin-8; Predictive Value of Tests

Diabetes mellitus is a systemic disease with several major complications affecting both the quality and length of life. One of these complications is periodontal disease (periodontitis). Periodontitis is much more than a localized oral infection. Recent data indicate that periodontitis may cause changes in systemic physiology. The interrelationships between periodontitis and diabetes provide an example of systemic disease predisposing to oral infection, and once that infection is established, the oral infection exacerbates systemic disease. In this case, it may also be possible for the oral infection to predispose to systemic disease. In order to understand the cellular/molecular mechanisms responsible for such a cyclical association, one must identify common physiological changes associated with diabetes and periodontitis that produce a synergy when the conditions coexist. A potential mechanistic link involves the broad axis of inflammation, specifically immune cell phenotype, serum lipid levels, and tissue homeostasis. Diabetes-induced changes in immune cell function produce an inflammatory immune cell phenotype (upregulation of proinflammatory cytokines from monocytes/polymorphonuclear leukocytes and downregulation of growth factors from macrophages). This predisposes to chronic inflammation, progressive tissue breakdown, and diminished tissue repair capacity. Periodontal tissues frequently manifest these changes because they are constantly wounded by substances emanating from bacterial biofilms. Diabetic patients are prone to elevated low density lipoprotein cholesterol and triglycerides (LDL/TRG) even when blood glucose levels are well controlled. This is significant, as recent studies demonstrate that hyperlipidemia may be one of the factors associated with diabetes-induced immune cell alterations. Recent human studies have established a relationship between high serum lipid levels and periodontitis. Some evidence now suggests that periodontitis itself may lead to elevated LDL/TRG. Periodontitis-induced bacteremia/endotoxemia has been shown to cause elevations of serum proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), which have been demonstrated to produce alterations in lipid metabolism leading to hyperlipidemia. Within this context, periodontitis may contribute to elevated proinflammatory cytokines/serum lipids and potentially to systemic disease arising from chronic hyperlipidemia and/o

Topics: Bacteremia; Bacterial Infections; Biofilms; Blood Glucose; Cholesterol, LDL; Diabetes Complications; Diabetes Mellitus; Disease Susceptibility; Down-Regulation; Endotoxemia; Growth Substances; Homeostasis; Humans; Hyperlipidemias; Inflammation; Inflammation Mediators; Insulin Resistance; Interleukin-8; Islets of Langerhans; Periodontitis; Phenotype; Risk Factors; Triglycerides; Tumor Necrosis Factor-alpha; Up-Regulation; Wound Healing

Recent advances in febrile neutropenia have highlighted the value of risk stratification especially that it can have important implications in terms of management. We aimed to identify a serum marker that may help to stratify febrile neutropenic pediatric patients treated for hematologic malignancies at the time of first evaluation. Thus, C-reactive protein (CRP), interleukin-8 (IL-8), and monocyte chemotactic protein-1-alpha (MCP-1-alpha) were evaluated for their predictive and diagnostic relevance in febrile episodes of cancer patients.. Within 24 hours of fever, CRP, IL-8, and MCP-1 serum levels were measured and the levels of these markers were related to the clinical findings of the patients. For this purpose, we collected and analyzed clinical data of 85 fever episodes occurring in 76 patients with hematologic malignancies, presenting to the Department of Pediatric Oncology, National Cancer Institute, Cairo University, during a 6-month period.. Neutropenic children with febrile episodes were classified into 2 groups, a group with unexplainable fever (group I, n=26) and another group with either blood culture positive, and/or fever periods with a documented clinical sepsis and/or local infection (group II, n=59). Clinically, local sites of infection were encountered in 39 cases (45.9%), whereas a positive blood culture was detected in 20 cases. CRP, IL-8, and MCP-1 levels were significantly lower in group I versus group II (P value <0.001). There were overlaps of values between groups. CRP > or =90 mg/L was significantly associated with chemotherapy-related neutropenia and fever owing to bacteremia (P=0.038). The sensitivity, specificity, negative and positive predictive values of CRP, MCP-1, and IL-8 were (70%, 73%, 51%, and 85%), (64%, 92%, 53%, and 95%), and (71%, 77%, 54%, and 88%), respectively. Combining 2 or 3 markers improved the diagnostic performance of these test, as 78% of group II had elevated 2 or 3 markers versus 16% of the group with no evident infection.. Low levels of CRP, MCP-1, and IL-8 could identify patients with unexplainable fever; whereas, high levels of these markers were of help in the diagnosis of infectious episodes. A model combining more than 1 marker is recommended in the assessment of febrile neutropenia.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; C-Reactive Protein; Chemokine CCL2; Child; Child, Preschool; Female; Fever; Hematologic Neoplasms; Humans; Infant; Interleukin-8; Leukemia; Male; Neutropenia; Predictive Value of Tests; Prognosis; Prospective Studies; Reference Values; Risk Factors; Treatment Outcome

Plasma interleukin-8 (IL-8) interleukin-10 (IL-10), and E-selectin concentrations were studied in 39 neutropenic and 30 non-neutropenic bacteremic patients; 54 nonbacteremic patients were analyzed as controls. Interleukin-8 concentrations were significantly higher in neutropenic than in non-neutropenic bacteremic patients (median 475 vs. 0 pg/ml, p < 0.0001). Median IL-8 and IL-10 levels were higher in bacteremic than in non-bacteremic patients (330 vs. 0 pg/ml, p < 0.0001 and 20 vs. 0 pg/ml, p = 0.04, respectively). In contrast, concentrations of IL-10 were similar in neutropenic and non-neutropenic patients. Median levels of E-selectin were not increased in any of the patient groups. Neutropenic bacteremic patients showed significantly lower concentrations of E-selectin than did non-neutropenic bacteremic patients (p < 0.0001). In conclusion, neutropenic bacteremic patients had significantly higher concentrations of IL-8 than non-neutropenic bacteremic patients. Levels of IL-10 were higher in bacteremic than in nonbacteremic patients, but neutropenic and non-neutropenic patients had similar levels of IL-10. Increased levels of E-selectin were not found in any of the patient groups, although neutropenic patients with bacteremia had lower concentrations than did non-neutropenic patients.

Topics: Adult; Aged; Bacteremia; Biomarkers; Chi-Square Distribution; E-Selectin; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Immunoenzyme Techniques; Interleukin-10; Interleukin-8; Male; Middle Aged; Neutropenia; Sensitivity and Specificity

The clinical significance of differences between antibiotics in endotoxin-liberating potential is unknown. Thirty patients with gram-negative urosepsis were randomized between imipenem and ceftazidime, which have, respectively, a low and a high endotoxin-liberating potential in vitro. In patients treated with ceftazidime, a slower defervescence was noticed. After 4 h of treatment, the blood endotoxin level decreased in all 3 endotoxemic patients receiving imipenem, whereas it increased in 2 of the 4 endotoxemic patients receiving ceftazidime, and in ceftazidime-treated patients, the endotoxin level in urine decreased less than in imipenem-treated subjects. Serum and urine cytokine levels increased 10%-40% after 4 h of ceftazidime treatment compared with no increase in the imipenem-treated patients (P > .05). Endotoxin release during antibiotic killing in vitro, assessed for all microorganisms, was 10-fold higher with ceftazidime (P < .001). These results indicate that differences between antibiotics in endotoxin release may affect the inflammatory response during treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Ceftazidime; Double-Blind Method; Endotoxins; Enterobacter cloacae; Escherichia coli; Gram-Negative Bacterial Infections; Humans; Imipenem; Interleukin-6; Interleukin-8; Klebsiella pneumoniae; Middle Aged; Prospective Studies; Pseudomonas aeruginosa; Tumor Necrosis Factor-alpha; Urinary Tract Infections

Non-Hodgkin's lymphoma (NHL) is a form of tumor that originates in the lymphoid tissues. Bacterial infections are very common in NHL patients. Because most of the patients do not experience apparent symptoms during the initial stage of infection, it is difficult to detect the underlying condition before it progresses to a more critical level. The activation of the cytokines is a hallmark of inflammation. Due to the advantages of short detection time and high sensitivity of cytokines, many studies have focused on relationship between cytokines and infection. However, few studies have been conducted on NHL patients with infection. Therefore, we reviewed the cytokine profiles of 229 newly diagnosed NHL patients and 40 healthy adults to predict respiratory bacterial infection and bacteremia. Our findings revealed that IL-6(41.67 vs 9.50 pg/mL), IL-8(15.55 vs 6.61 pg/mL), IL-10(8.02 vs 4.52 pg/mL),TNF-β(3.82 vs 2.96 pg/mL), IFN- γ(4.76 vs 2.96 pg/mL), body temperature(37.6 vs 36.5°C), CRP(20.80 vs 4.37 mg/L), and PCT(0.10 vs 0.04 ng/mL) levels were considerably greater in NHL cases with respiratory bacterial infections relative to NHL cases without infection (P<0.05). Furthermore, IL-6(145.00 vs 41.67 pg/mL), IL-8(34.60 vs 15.55 pg/mL),temperature(38.4 vs 37.6°C), PCT(0.79 vs 0.10 ng/mL), and CRP(93.70 vs 20.80 mg/L) levels in respiratory infectious NHL patients with more severe bacteremia were considerably elevated than in patients with respiratory bacterial infections only (P<0.05). Remarkably, increased levels of IL-6 and IL-8 are effective in determining whether or not pulmonary bacterial infectious NHL patients have bacteremia. Temperature, PCT, and CRP all have lower sensitivity and specificity than IL-6. IL-6 ≥18.79pg/mL indicates the presence of pulmonary bacterial infection in newly diagnosed NHL patients, and IL-6 ≥102.6pg/mL may suggest pulmonary bacterial infection with bacteremia. In short, this study shows that cytokines can be advantageous in the diagnosis and differentiation of pulmonary bacterial infection and bacteremia in newly diagnosed NHL patients and may also guide for the use of clinical antibiotics.

Topics: Adult; Bacteremia; Bacterial Infections; Cytokines; Humans; Interleukin-6; Interleukin-8; Lymphoma, Non-Hodgkin; Respiratory Tract Infections

Sepsis is a syndrome where the dysregulated host response to infection threatens the life of the patient. The isoform of the cholesteryl-ester transfer protein (CETPI) is synthesized in the small intestine, and it is present in human plasma. CETPI and peptides derived from its C-terminal sequence present the ability to bind and deactivate bacterial lipopolysaccharides (LPS). The present study establishes the relationship between the plasma levels of CETPI and disease severity of sepsis due to Gram-negative bacteria.. Plasma samples from healthy subjects and patients with positive blood culture for Gram-negative bacteria were collected at the Intensive Care Unit (ICU) of INCMNSZ (Mexico City). 47 healthy subjects, 50 patients with infection, and 55 patients with sepsis and septic shock, were enrolled in this study. CETPI plasma levels were measured by an enzyme-linked immunosorbent assay and its expression confirmed by Western Blot analysis. Plasma cytokines (IL-1β, TNFα, IL-6, IL-8, IL-12p70, IFNγ, and IL-10) were measured in both, healthy subjects, and patients, and directly correlated with their CETPI plasma levels and severity of clinical parameters. Sequential Organ Failure Assessment (SOFA) scores were evaluated at ICU admission and within 24 h of admission. Plasma LPS and CETPI levels were also measured and studied in patients  with liver dysfunction.. The level of CETPI in plasma was found to be higher in patients with positive blood culture for Gram-negative bacteria that in control subjects, showing a direct correlation with their SOFA values. Accordingly, septic shock patients showing a high CETPI plasma concentration, presented a negative correlation with cytokines IL-8, IL-1β, and IL-10. Also, in patients  with liver dysfunction, since higher CETPI levels correlated with a high plasma LPS concentration, LPS neutralization carried out by CETPI might be considered a physiological response that will have to be studied in detail.. Elevated levels of plasma CETPI were associated with disease severity and organ failure in patients  with Gram-negative bacteraemia, defining CETPI as a protein implicated in the systemic response to LPS.

Topics: Bacteremia; Cholesterol Ester Transfer Proteins; Cytokines; Esters; Humans; Interleukin-10; Interleukin-8; Lipopolysaccharides; Peptides; Protein Isoforms; Sepsis; Shock, Septic

The study aimed to analyze morphological and functional changes of

Topics: Adult; Allylbenzene Derivatives; Anisoles; Anti-Bacterial Agents; Antioxidants; Bacteremia; Blood Cell Count; Female; Humans; Immunity, Innate; Interleukin-8; Male; Nitroblue Tetrazolium; Phagocytes; Phagocytosis; Spectroscopy, Fourier Transform Infrared; Staphylococcal Infections; Staphylococcus aureus; Xanthophylls

Unassisted metastasis through the lymphatic system is a mechanism of dissemination thus far ascribed only to cancer cells. Here, we report that Streptococcus pyogenes also hijack lymphatic vessels to escape a local infection site, transiting through sequential lymph nodes and efferent lymphatic vessels to enter the bloodstream. Contrasting with previously reported mechanisms of intracellular pathogen carriage by phagocytes, we show S. pyogenes remain extracellular during transit, first in afferent and then efferent lymphatics that carry the bacteria through successive draining lymph nodes. We identify streptococcal virulence mechanisms important for bacterial lymphatic dissemination and show that metastatic streptococci within infected lymph nodes resist and subvert clearance by phagocytes, enabling replication that can seed intense bloodstream infection. The findings establish the lymphatic system as both a survival niche and conduit to the bloodstream for S. pyogenes, explaining the phenomenon of occult bacteraemia. This work provides new perspectives in streptococcal pathogenesis with implications for immunity.

Topics: Animals; Bacteremia; Disease Models, Animal; Female; Interleukin-8; Lymph Nodes; Lymphatic Metastasis; Lymphatic System; Lymphatic Vessels; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neutrophils; Phagocytosis; Streptococcal Infections; Streptococcus pyogenes; Virulence

Staphylococcus aureus is a leading cause of bacteremia, yet there remains a significant knowledge gap in the identification of relevant biomarkers that predict clinical outcomes. Heterogeneity in the host response to invasive S. aureus infection suggests that specific biomarker signatures could be utilized to differentiate patients prone to severe disease, thereby facilitating earlier implementation of more aggressive therapies.. To further elucidate the inflammatory correlates of poor clinical outcomes in patients with S. aureus bacteremia, we evaluated the association between a panel of blood proteins at initial presentation of bacteremia and disease severity outcomes using 2 cohorts of patients with S. aureus bacteremia (n = 32 and n = 124).. We identified 13 candidate proteins that were correlated with mortality and persistent bacteremia. Prognostic modeling identified interleukin (IL)-8 and CCL2 as the strongest individual predictors of mortality, with the combination of these biomarkers classifying fatal outcome with 89% sensitivity and 77% specificity (P < .0001). Baseline IL-17A levels were elevated in patients with persistent bacteremia (P < .0001), endovascular (P = .026) and metastatic tissue infections (P = .012).. These results demonstrate the potential utility of selected biomarkers to distinguish patients with the highest risk for treatment failure and bacteremia-related complications, providing a valuable tool for clinicians in the management of S. aureus bacteremia. Additionally, these biomarkers could identify patients with the greatest potential to benefit from novel therapies in clinical trials.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Biomarkers; Case-Control Studies; Chemokine CCL2; Endocarditis, Bacterial; Female; Humans; Interleukin-17; Interleukin-8; Male; Middle Aged; Prognosis; Sensitivity and Specificity; Severity of Illness Index; Staphylococcal Infections; Staphylococcus aureus; Survival Analysis

Despite improvements in diagnosis and treatment, infections are still a major cause of morbidity and mortality in children with febrile neutropenia. In the majority of febrile episodes, the source of infection cannot be defined. In this study, we aimed to identify the earlier predictors of bacteremia/fungemia and a useful cytokine to identify the source of infection and to discriminate the patients with culture-confirmed bacterial/fungal infection. The most sensitive cytokine was interleukin (IL)-10 and the most specific was IL-8 in predicting culture-confirmed cases. IL-8 had greater sensitivity and specificity in determination of gram-negative bacterial infections with a higher negative predictive value; therefore, IL-8 can be used particularly to rule out gram-negative bacterial infections. IL-6, IL-8, and IL-10 circulating levels were shown to be higher in cases of infection. Further studies are needed to recommend a routine practice for predicting culture-confirmed bacterial infections.. Tanı ve tedavideki gelişmelere rağmen, febril nötropenili çocuklarda enfeksiyonlar morbidite ve mortalitenin önemli bir nedenidir. Febril nötropeni epizodlarının çoğunluğunda enfeksiyon odağı belirlenememektedir. Bu çalışmada, enfeksiyon odağını ve kültürle kanıtlanmış bakteriyel ve fungal enfeksiyonlarını belirlemede daha erken belirteçler bulunması amaçlanmıştır. Kültür ile kanıtlanmış enfeksiyonları belirlemede en hassas sitokin interlökin (IL)-10 ve en özgül sitokin IL-8’dir. Gram-negatif bakteriyel enfeksiyonları belirlemede en hassas ve özgül sitokin IL-8’dir ve IL-8’in negatif prediktif değerinin yüksek olması nedeniyle, özellikle gram-negatif bakteriyel enfeksiyonları dışlamada kullanılabilir. IL-6, IL-8, IL-10’un kan düzeyleri enfeksiyon durumunda daha yüksek saptanmıştır. Sitokinlerin kültür ile kanıtlanmış enfeksiyonları belirlemede rutin kullanımını önermek için gelecekte yapılacak çalışmalara ihtiyaç vardır.

Topics: Bacteremia; Child; Child, Preschool; Febrile Neutropenia; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Interleukin-10; Interleukin-6; Interleukin-8; Male

Febrile urinary tract infection (UTI) is a common bacterial disease that may lead to substantial morbidity and mortality especially among the elderly. Little is known about biomarkers that predict a complicated course. Our aim was to determine the role of certain urinary cytokines or antimicrobial proteins, plasma vitamin D level, and genetic variation in host defense of febrile UTI and its relation with bacteremia.. A case-control study. Out of a cohort of consecutive adults with febrile UTI (n = 787) included in a multi-center observational cohort study, 46 cases with bacteremic E.coli UTI and 45 cases with non-bacteremic E.coli UTI were randomly selected and compared to 46 controls. Urinary IL-6, IL-8, LL37, β-defensin 2 and uromodulin as well as plasma 25-hydroxyvitamin D were measured. In 440 controls and 707 UTI patients polymorphisms were genotyped in the genes CXCR1, DEFA4, DEFB1, IL6, IL8, MYD88, UMOD, TIRAP, TLR1, TLR2, TLR5 and TNF.. IL-6, IL-8, and LL37 are different between controls and UTI patients, although these proteins do not distinguish between patients with and without bacteremia. While uromodulin did not differ between groups, inability to produce uromodulin is more common in patients with bacteremia. Most participants in the study, including the controls, had insufficient vitamin D and, at least in winter, UTI patients have lower vitamin D than controls. Associations were found between the CC genotype of IL6 SNP rs1800795 and occurrence of bacteremia and between TLR5 SNP rs5744168 and protection from UTI. The rare GG genotype of IL6 SNP rs1800795 was associated with higher β-defensin 2 production.. Although no biomarker was able to distinguish between UTI with or without bacteremia, two risk factors for bacteremia were identified. These were inability to produce uromodulin and an IL6 rs1800795 genotype.

Topics: Adult; Aged; Aged, 80 and over; Antimicrobial Cationic Peptides; Bacteremia; beta-Defensins; Case-Control Studies; Cathelicidins; Female; Fever; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Polymorphism, Genetic; Risk Factors; Urinary Tract Infections; Uromodulin; Vitamin D

Bacterial involvement is believed to play a pivotal role in the development and disease outcome of NEC. However, whether a bloodstream infection (BSI) predisposes to NEC (e.g. by activating the pro-inflammatory response) or result from the loss of gut wall integrity during NEC development is a longstanding question.. We hypothesize that the occurrence of a BSI plays a complementary role in the pathogenesis of NEC. The first aim of the study was to correlate the occurrence of a BSI during the early phase of NEC with intestinal fatty acid-binding protein (I-FABP) levels, as a marker for loss of gut wall integrity owing to mucosal damage, and Interleukin (IL)-8 levels, as a biomarker for the pro-inflammatory cascade in NEC. The second aim of the study was to investigate the relation between the occurrence of a BSI and disease outcome.. We combined data from prospective trials from two large academic pediatric surgical centers. Thirty-eight neonates with NEC, 5 neonates with bacterial sepsis, and 14 controls were included.. BSIs occurred in 10/38 (26%) neonates at NEC onset. No association between the occurrence of BSIs and I-FABP levels in plasma (cohort 1: median 11ng/mL (range 0.8-298), cohort 2: median 6.8ng/mL (range 1.3-15)) was found in NEC patients (cohort 1: p=0.41; cohort 2: p=0.90). In addition, the occurrence of BSIs did not correlate with IL-8 (median 1562pg/mL (range 150-7,500); p=0.99). While the occurrence of a BSI was not correlated with Bell's stage (p=0.85), mortality was higher in patients with a BSI (p=0.005).. The low incidence of BSIs and the absent association of both the markers for loss of gut wall integrity and the pro-inflammatory response during the early phase of NEC, support the hypothesis that the presence of a BSI does not precede NEC.

Topics: Bacteremia; Biomarkers; Enterocolitis, Necrotizing; Fatty Acid-Binding Proteins; Female; Humans; Incidence; Infant, Newborn; Interleukin-8; Male; Prospective Studies

Even though Arcobacter butzleri has been implicated in some human disease as diarrhoea and bacteraemia, much of its pathogenesis and virulence factors remain unclear. In this work we have compared pathogenic and genotypic properties of six A. butzleri isolates from human and non-human sources. The tested isolates showed to be susceptible to tetracyclines and aminoglycosides, however non-human isolates were all resistant to quinolones. The ability to form biofilms was variable among the tested strains, and all of them showed a weak haemolytic activity. The presence of nine putative virulence genes was determined, with cadF, ciaB, cj1349, mviN, pldA, tlyA being detected in all strains, while irgA (3/6), hecA (5/6), hecB (4/6) were detected only in some strains. High levels of adhesion were observed for A. butzleri on Caco-2 cells, with pre-existing inflammation showing no significant effect on the adherence ability; yet variable levels of invasion were observed. A. butzleri isolates were able to survive intracellularly in Caco-2 cells and to induce a significant up-regulation of interleukin-8 secretion and structural cell rearrangements. These data brings new insights on A. butzleri virulence and highlights its pathogenic potential.

Topics: Anti-Bacterial Agents; Arcobacter; Bacteremia; Bacterial Adhesion; Biofilms; Caco-2 Cells; Diarrhea; DNA, Bacterial; Epithelial Cells; Genes, Bacterial; Genotype; Hemolysis; Humans; Interleukin-8; Microbial Sensitivity Tests; Phenotype; Polymerase Chain Reaction; Virulence Factors

Topics: Bacteremia; C-Reactive Protein; Child; Febrile Neutropenia; Hematopoietic Stem Cell Transplantation; Humans; Immunization, Passive; Interleukin-8

Despite a low bacteremia rate, pediatric oncology patients are frequently admitted for febrile neutropenia. A pediatric risk prediction model with high sensitivity to identify patients at low risk for bacteremia is not available. We performed a single-institution prospective cohort study of pediatric oncology patients with febrile neutropenia to create a risk prediction model using clinical factors, respiratory viral infection, and cytokine expression.. Pediatric oncology patients with febrile neutropenia were enrolled between March 30, 2010 and April 1, 2011 and managed per institutional protocol. Blood samples for C-reactive protein and cytokine expression and nasopharyngeal swabs for respiratory viral testing were obtained. Medical records were reviewed for clinical data. Statistical analysis utilized mixed multiple logistic regression modeling.. During the 12-month period, 195 febrile neutropenia episodes were enrolled. There were 24 (12%) episodes of bacteremia. Univariate analysis revealed several factors predictive for bacteremia, and interleukin (IL)-8 was the most predictive variable in the multivariate stepwise logistic regression. Low serum IL-8 predicted patients at low risk for bacteremia with a sensitivity of 0.9 and negative predictive value of 0.98.. IL-8 is a highly sensitive predictor for patients at low risk for bacteremia. IL-8 should be utilized in a multi-institution prospective trial to assign risk stratification to pediatric patients admitted with febrile neutropenia.

Topics: Adolescent; Adult; Bacteremia; Bacteria; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; Infant; Interleukin-8; Male; Neoplasms; Neutropenia; Prognosis; Prospective Studies; Risk Factors; ROC Curve; Young Adult

The endotoxin activity assay (EAA) is a FDA-approved blood endotoxin assay that is reported as a useful tool for the diagnosis of gram-negative bacterial infection. However, discrepancies between the results of the EAA and those of the limulus amebocyte lysate (LAL) assay have been reported. Thus, we verified these methods. Blood was incubated with anti-endotoxin antibody, the resultant polymorphonuclear activation to produce oxidants was measured and the EAA level calculated. As a reference endotoxin assay, we used an endotoxin-specific LAL assay. Significant increases in plasma LAL assay levels were observed only in patients with sepsis caused by gram-negative bacterial infections, whereas higher EAA levels were observed in almost all the sepsis cases and the SIRS cases, especially those with acute pancreatitis. Graded amounts of LPS (1-10,000 pg/ml) were spiked into normal blood to obtain dose-response curves: a good dose-response curve, from 1 to 1,000 pg/ml, was obtained for the LAL assay. A good dose-response curve was barely obtained for the EAA; the lowest detection limit seemed to be 1,000 pg/ml. Addition of methylprednisolone decreased the EAA levels. Interleukin-8 (IL-8) induced elevation in EAA levels when IL-8 was added to volunteers' blood samples. Overall, the EAA kit could not measure clinically relevant doses of endotoxin. Because IL-8 induced an increase in EAA level, it is suggested that the EAA level reflects the primed state of polymorphonuclear leukocytes.

Topics: Bacteremia; Bacteriological Techniques; Dose-Response Relationship, Drug; Endotoxins; Humans; Interleukin-8; Limulus Test; Methylprednisolone; Neutrophils; Reproducibility of Results; Systemic Inflammatory Response Syndrome

Biomarkers and physiomarkers may be useful adjunct tests for sepsis detection in neonatal intensive care unit (NICU) patients. We studied whether measuring plasma cytokines at the time of suspected sepsis could identify patients with bacteremia in centers in which patients were undergoing continuous physiomarker screening using a heart rate characteristics (HRC) index monitor.. Six cytokines were higher in Gram-negative bacteremia (GNB) than in Gram-positive bacteremia or candidemia (GPBC). A cytokine score using thresholds for granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α had 100% sensitivity and 69% positive predictive value (PPV) for GNB. A single cytokine marker, IL-6 < 130 pg/ml, had 100% sensitivity and 52% PPV for sepsis ruled out (SRO). The average HRC index was abnormal in this cohort of patients with clinical suspicion of sepsis and did not discriminate between the final sepsis designations.. In summary, in NICU patients with suspected late-onset sepsis, plasma cytokines can identify those with SRO and those with GNB, potentially aiding in decisions regarding therapy.. Seven cytokines were measured in 226 plasma samples from patients >3 d old with sepsis suspected based on clinical signs, abnormal HRC index, or both. Cases were classified as SRO, clinical sepsis (CS), GPBC, or GNB.

Topics: Bacteremia; Biomarkers; Cytokines; Diagnosis, Differential; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Granulocyte Colony-Stimulating Factor; Heart Rate; Humans; Infant, Newborn; Inpatients; Intensive Care Units, Neonatal; Interleukin-6; Interleukin-8; Neonatal Screening; Retrospective Studies; Sensitivity and Specificity; Tumor Necrosis Factor-alpha

Early diagnosis of sepsis in children with febrile neutropenia and cancer still remains a challenge for modern medicine because of lack of specific laboratory markers and clinical signs especially at the beginning of the infection. The objective of this study was to evaluate the ability of interleukin-6 and interleukin-8 to predict bacteremia and sepsis during the first 2 days in oncohematologic patients with febrile neutropenia.. A total of 61 febrile neutropenic episodes in 37 children were studied. Serum samples were collected on day 1 and day 2 from the onset of fever and analyzed using an automated random access analyzer.. Neutropenic children with febrile episodes were classified into the following 2 groups: (1) fever of unknown origin group--patients with a negative blood culture--and (2) bacteremia/sepsis group--patients with a positive blood culture or clinical sepsis. High negative predictive values were found on day 1 for interleukin-6 and interleukin-8 (89% and 82%, respectively) for exclusion of bacteremia/sepsis.. These interleukins could be used as a screening tool for the rejection of sepsis or bacteremia on the first day of fever in neutropenic children with cancer.

Topics: Adolescent; Bacteremia; Biomarkers; Child; Child, Preschool; Diagnosis, Differential; Female; Fever; Humans; Infant; Interleukin-6; Interleukin-8; Male; Neoplasms; Neutropenia; Sepsis

The aim of this study was to test the predictive value of interleukin (IL) 8 in the assessment of intestinal involvement in necrotizing enterocolitis (NEC).. Forty infants with surgically treated NEC were classified into 3 groups based on intestinal involvement during laparotomy: focal (n = 11), multifocal (n = 16), and panintestinal (n = 13). Preoperatively obtained serum levels of IL-8, C-reactive protein, white blood cell count, and platelet count were correlated with intestinal involvement using logistic regression models.. Interleukin 8 correlated significantly with intestinal involvement in infants with surgically treated NEC (odds ratio, 1.74; confidence interval, 1.27-2.39; P < .001). An exploratory IL-8 cutoff value of 449 pg/mL provided a specificity of 81.8% and sensitivity of 82.8% to discriminate focal from multifocal and panintestinal disease. An IL-8 cutoff value of 1388 pg/mL provided a specificity of 77.8% and a sensitivity of 76.9% to discriminate panintestinal disease from focal and multifocal disease.. To our knowledge, this is the first study to demonstrate a significant correlation of IL-8 with intestinal involvement in advanced NEC in a large patient population. Our results indicate that IL-8 may be a promising biomarker for assessing intestinal involvement in infants with advanced NEC.

Topics: Bacteremia; Biomarkers; C-Reactive Protein; Enterocolitis, Necrotizing; Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-8; Intestines; Laparotomy; Leukocyte Count; Male; Pneumatosis Cystoides Intestinalis; Predictive Value of Tests; Preoperative Care; ROC Curve; Sensitivity and Specificity; Severity of Illness Index

Bacteremia is one of the most important causes of morbidity and mortality in cancer patients. The aim of this study was to evaluate the diagnostic usefulness of procalcitonin (PCT), interleukin 8 (IL-8), interleukin 6 (IL-6), and C-reactive protein (CRP) in the detection of bacteremia in cancer patients.. PCT, IL-8, IL-6, and CPR levels were measured in 2 groups of cancer patients who had fever: one group with true bacteremia and another without bacteremia.. Seventy-nine febrile episodes were analyzed in 79 patients, 43 men and 36 women. Forty-four patients were in the true bacteremia group. Significant differences in PCT (P<0.001), IL-8 (P<0.001), and IL-6 (P=0.002) values were found between patients with and without true bacteremia. CPR results were not significantly different between the groups (P=0.23). The cut-off point for PCT was 0.5 ng/mL and this parameter yielded the best specificity at 91.4%, with a sensitivity of 59.1%.. Among the infection markers studied, PCT provided the most information for diagnosing bacteremia in cancer patients.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fungemia; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Neoplasms; Prospective Studies; Protein Precursors

Assay of cytokines and C reactive protein (CRP) in different periods of febrile neutropenia may be helpful for early defining the risk in severe infections. We determined serum interleukin-6 (IL-6), interleukin-8 (IL-8), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and CRP in 22 previously untreated patients with various malignancies. Samples were obtained in four different clinical periods of febrile neutropenia; prior to chemotherapy, afebrile neutropenic period after chemotherapy, febrile neutropenic period, and recovery period. When compared to sex-and age-matched group of healthy subjects, IL-6, IL-8, sIL-2R, and CRP levels were found to be elevated in all periods. The highest levels were encountered in the febrile neutropenic period. For predictivity purposes, the afebrile neutropenic period was the most important period. Serum sIL-2R, IL-6, IL-8 and CRP levels were elevated in this period. IL-8 levels showed the most stable elevation through different stages of febrile neutropenia. Serum IL-8 levels were found to have the most reliable and stable elevation in different clinical stages of febrile neutropenia. Nevertheless, IL-8 is not able to discriminate among risk groups and cannot be used as a predictive factor.

Topics: Adult; Aged; Bacteremia; Biomarkers; C-Reactive Protein; Candidiasis; Cytokines; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Neutropenia; Receptors, Interleukin-2; Tumor Necrosis Factor-alpha

Based on the implication of soluble triggering receptor expressed on myeloid cells (sTREM-1) in the septic cascade, it was investigated whether it participates or not in posttraumatic systemic inflammatory response syndrome (SIRS).. Blood was sampled on days 1, 4, 7, and 15 from 69 patients with SIRS after multiple injuries and upon presentation of a septic complication. Concentrations of sTREM-1, tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-8, and interferon-gamma were determined by an enzyme immunoassay. Samples drawn on day 1 from 10 trauma patients without SIRS served as controls.. In 26 patients with SIRS without septic complication, sTREM-1, TNFalpha, and IL-8 remained stable over follow-up; IL-6 decreased and interferon-gamma increased on days 4 and 7 compared with day 1. TNFalpha was the only variable being higher upon advent of septic shock compared with patients without SIRS and upon presentation of SIRS, sepsis, and severe sepsis (p of comparisons with all subgroups <0.0001). Mortality of patients with sTREM-1 greater than 180 pg/mL was 5.3% compared with 28.0% of those with sTREM-1 lower than 180 pg/mL (p 0.035). sTREM-1 higher than 40 pg/mL had sensitivity 56.5% and specificity 91.7% for the differential diagnosis between SIRS and sepsis after multiple injuries.. This is the first study providing evidence about the participation of sTREM-1 in posttraumatic SIRS. Its levels are increased and remain constant over time in patients who did not develop any complications whereas it seems to behave as an anti-inflammatory mediator.

Topics: Adult; Aged; Bacteremia; Cross Infection; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Gram-Negative Bacterial Infections; Humans; Injury Severity Score; Interferon-gamma; Interleukin-6; Interleukin-8; Male; Membrane Glycoproteins; Middle Aged; Multiple Organ Failure; Multiple Trauma; Pneumonia, Bacterial; Predictive Value of Tests; Prognosis; Prospective Studies; Pyelonephritis; Receptors, Immunologic; Shock, Septic; Systemic Inflammatory Response Syndrome; Time Factors; Triggering Receptor Expressed on Myeloid Cells-1; Tumor Necrosis Factor-alpha

In this study we tested how a combination of early and late paraclinic markers could predict early onset neonatal sepsis (EONS).. The first 24 hours after the suspicion of EONS, we measured interleukine (IL)-6, IL-8, IL-10, IL-18, tumor necrosis factor-alpha (TNF-alpha), interferon gamma (INF-gamma), procalcitonin (PCT) and C-reactive protein (CRP) at 8-hour intervals on 123 neonates clinically suspected for EONS. The neonates were divided into two groups. The sepsis group: 1A with blood culture verified bacteraemia and 1B strongly suspected sepsis (29 patients). The no sepsis group: 2A treated with antibiotics (37 patients) and 2B not treated with antibiotics (57 patients).. Combined evaluation of each of the early markers with PCT > 25 ng/ml for prediction of EONS at time 0, gave the following sensitivities and specificities: IL-6 > 250 pg/ml: 71% and 88%; IL-8 > 900 pg/ml: 50% and 88%; IL-10 > 40 pg/ml: 43% and 87%; and immature/total (I/T) ratio > 0.35: 59% and 88%. The results of IL-18, TNF-alpha and IFN-gamma did not predict EONS.. IL-6 combined with PCT values is a fair way to evaluate EONS at the time of suspicion of infection. The "old" early marker, I/T ratio, is almost as efficient as IL-6. By combining an early and a late marker it may be possible to reduce the diagnostic "non-conclusive" period of paraclinic values.

Topics: Anti-Bacterial Agents; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Escherichia coli Infections; Female; Humans; Infant, Newborn; Inflammation Mediators; Interferon-gamma; Interleukin-10; Interleukin-18; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Neutrophils; Protein Precursors; Retrospective Studies; Sensitivity and Specificity; Sepsis; Staphylococcal Infections; Streptococcal Infections; Streptococcus agalactiae; Tumor Necrosis Factor-alpha

Stenotrophomonas maltophilia is a multiple-antibiotic-resistant opportunistic pathogen that is being isolated with increasing frequency from patients with health-care-associated infections and especially from patients with cystic fibrosis (CF). While clinicians feel compelled to treat infections involving this organism, its potential for virulence is not well established. We evaluated the immunostimulatory properties and overall virulence of clinical isolates of S. maltophilia using the well-characterized opportunistic pathogen Pseudomonas aeruginosa PAO1 as a control. The properties of CF isolates were examined specifically to see if they have a common phenotype. The immunostimulatory properties of S. maltophilia were studied in vitro by stimulating airway epithelial and macrophage cell lines. A neonatal mouse model of pneumonia was used to determine the rates of pneumonia, bacteremia, and mortality, as well as the inflammatory response elicited by S. maltophilia infection. Respiratory and nonrespiratory S. maltophilia isolates were highly immunostimulatory and elicited significant interleukin-8 expression by airway epithelial cells, as well as tumor necrosis factor alpha (TNF-alpha) expression by macrophages. TNF-alpha signaling appears to be important in the pathogenesis of S. maltophilia infection as less than 20% of TNFR1 null mice (compared with 100% of wild-type mice) developed pneumonia and bacteremia following intranasal inoculation. The S. maltophilia isolates were weakly invasive, and low-level bacteremia with no mortality was observed. Despite the lack of invasiveness of S. maltophilia, the immunostimulatory properties of this organism and its induction of TNF-alpha expression specifically indicate that it is likely to contribute significantly to airway inflammation.

Topics: Animals; Bacteremia; Cell Line; Cystic Fibrosis; Epithelial Cells; Gram-Negative Bacterial Infections; Humans; Interleukin-8; Lipid A; Macrophages; Mice; Mice, Inbred C57BL; Mice, Transgenic; Phagocytosis; Pneumonia, Bacterial; Pseudomonas aeruginosa; Receptors, Tumor Necrosis Factor, Type I; Respiratory Mucosa; Respiratory Tract Infections; Stenotrophomonas maltophilia; Tumor Necrosis Factor-alpha

Despite bacteraemia is present in the majority of patients with pneumococcal, little is known about the influence of the systemic infection on the meningeal inflammatory response.. To explore the role of systemic infection on the meningeal inflammation, experimental meningitis was induced by intracisternal injection of approximately 1 x 10(6) CFU Streptococcus pneumoniae, type 3, and the 26 rabbits were either provided with approximately 1 x 10(6) CFU S. pneumoniae intravenously at 0 hour ("bacteraemic" rabbits, n = 9), immunized with paraformaldehyde-killed S. pneumoniae for 5 weeks prior to the experiment ("immunized" rabbits", n = 8), or not treated further ("control" rabbits, n = 9). WBC and bacterial concentrations were determined in CSF and blood every second hour during a 16 hours study period together with CSF IL-8 and protein levels. We also studied CSF and blood WBC levels in 153 pneumococcal meningitis patients with and without presence of bacteraemia.. As designed, blood bacterial concentrations were significantly different among three experimental groups during the 16 hours study period (Kruskal Wallis test, P < 0.05), whereas no differences in CSF bacterial levels were observed (P > 0.05). Blood WBC decreased in bacteraemic rabbits between approximately 10-16 hours after the bacterial inoculation in contrast to an increase for both the immunized rabbits and controls (P < 0.05). The CSF pleocytosis was attenuated in bacteraemic rabbits as compared to the two other groups between 12-16 hours from time of infection (P < 0.017), despite accelerated CSF IL-8 levels in bacteraemic rabbits. In patients with pneumococcal meningitis, no significant difference in CSF WBC was observed between patients with or without bacteraemia at admission (n = 103, 1740 cells/microL (123-4032) vs. n = 50, 1961 cells/microL (673-5182), respectively, P = 0.18), but there was a significant correlation between CSF and blood WBC (n = 127, Spearman rho = 0.234, P = 0.008).. Our results suggest that a decrease in peripheral WBC induced by enhanced bacteraemia in pneumococcal meningitis results in an attenuated CSF pleocytosis.

Topics: Animals; Bacteremia; Bacterial Vaccines; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Humans; Inflammation; Interleukin-8; Leukocyte Count; Leukocytosis; Meningitis, Pneumococcal; Rabbits; Streptococcus pneumoniae

Bacteremia frequently occurs after dental treatment. Periodontal inflammation may influence the incidence, magnitude and duration of bacteremia. The presence of circulating oral bacteria or bacterial components may induce cytokine synthesis in blood cells, which may contribute to the development or exacerbation of atherosclerosis. The present study tested the hypothesis that bacteremia occurring after scaling in periodontitis patients results in altered plasma levels of cytokines. Twenty periodontitis patients were subjected to scaling. Blood samples at baseline and at 0.5, 10 and 30 minutes postscaling were examined for bacteremia whereas baseline and eight-hour postscaling blood samples were examined for the levels of IL-1beta, TNF-alpha, IL-6, IL-8, IL-10 and IL-12p70. IL-6 levels were significantly increased eight hours after scaling, while IL-8 was significantly decreased. No systematic changes occurred in the levels of IL-1beta, TNF-alpha, IL-10 and IL-2p70. IL-6 levels may be increased while IL-8 may be decreased due to scaling, which may have implications for general health.

Topics: Adult; Bacteremia; Bacteroidaceae Infections; Dental Plaque Index; Dental Scaling; Female; Follow-Up Studies; Gingival Hemorrhage; Humans; Interleukin-10; Interleukin-12; Interleukin-6; Interleukin-8; Male; Middle Aged; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Prevotella; Streptococcal Infections; Streptococcus; Time Factors; Tumor Necrosis Factor-alpha

Chemokines are important in regulating leukocyte traffic during infection. We analyzed plasma chemokine levels of monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 alpha , interleukin (IL)-8, and RANTES in patients with meningococcal infection and correlated these to plasma lipopolysaccharide (LPS) levels, which are closely associated with clinical presentation. In patients with fulminant meningococcal septicemia, versus distinct meningitis or mild systemic meningococcal disease, MCP-1 (both P<.0001), MIP-1 alpha (both P<.0001), and IL-8 (P<.0001 and P=.011) were significantly higher and RANTES significantly lower (P=.007 and P=.021). MCP-1 (r=.88), MIP-1 alpha (r=.82), and IL-8 (r=.89) were positively correlated to plasma LPS levels, whereas RANTES was negatively correlated (r=-.49). In an ex vivo whole-blood model, heat-inactivated wild-type Neisseria meningitidis, purified meningococcal LPS, and (to a negligible extent) heat-inactivated LPS-deficient mutant N. meningitidis induced these chemokines. N. meningitidis LPS is the major cause of chemokine release in meningococcal disease.

Topics: Bacteremia; Chemokine CCL2; Chemokine CCL4; Chemokine CCL5; Chemokines; Gene Expression; Humans; Interleukin-8; Lipopolysaccharides; Macrophage Inflammatory Proteins; Meningococcal Infections; Neisseria meningitidis; Time Factors

Previous studies have shown that interleukin-8 serum levels in febrile neutropenic patients are significantly higher in patients with gram-negative bacteremia than in patients with other causes of fever and may indicate unfavorable outcomes. We assessed the value of interleukin-8 serum levels at fever onset to predict clinical complications in order to confirm these earlier findings.. In a prospective observational study of adult patients receiving cancer chemotherapy, serum samples obtained at the onset of 147 febrile neutropenic episodes were measured by an immunoluminescence assay.. Complicated courses of fever including severe sepsis or septic shock, respiratory insufficiency or death were observed in 13 episodes (9%); in six episodes complications had developed within 1 week after fever onset and five of them were associated with bloodstream infections. At an interleukin-8 cutoff level of 1,000 pg/ml, these early complications were predicted with a sensitivity of 83%, a specificity of 97%, a positive predictive value of 50%, and a negative predictive value of 99%, respectively.. Interleukin-8 levels at fever onset may be used for the prediction of early medical complications associated with bacteremia and can help identify patients who might benefit from intensive care admission.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Bacteremia; Fever; Gram-Negative Bacterial Infections; Humans; Interleukin-8; Middle Aged; Neutropenia; Predictive Value of Tests; Prognosis; Prospective Studies

To compare serum levels of interleukin-6, interleukin-8 and interleukin-10 in bacteremic and non-bacteremic episodes of febrile neutropenia in children with malignant diseases, and determine their changes and correlation with C-reactive protein (CRP).. Between January 2003 and June 2004, we examined 41 episodes of febrile neutropenia in 24 children with malignant diseases who were receiving polychemotherapy. C-reactive protein was measured at the onset of febrile episodes and on days 3 and 5 from beginning of therapy. The soluble interleukins-6, -8, and -10 were determined in the serum using enzyme bound immunosorbent analysis at the onset of fever and at 24 and 72 hours after initiation of an empiric antibiotic therapy.. The CRP baseline levels differentiated the patients with unexplained fever from those with local infection but did not differentiate them from those with bacteremia. Interleukin-8 at 24 hours differentiated bacteremic from non-bacteremic episodes (P < 0.05) and at a cut-off value of 130 pg/ml it had a sensitivity of 72% and a specificity of 84% to differentiate bacteremia. Interleukin-10 at 24 hours yielded higher values in Gram (-) bacteremia in comparison with the non-bacteremic episodes (P < 0.001) and Gram (+) bacteremia (P < 0.05). Interleukin-6 at 24 hours had significantly higher values in febrile episodes of more than 3 days duration (P < 0.05).. Interleukin-8 could differentiate in the first 24 hours bacteremic from non-bacteremic episodes in febrile neutropenia, while interleukin-10 is perhaps a more accurate marker for Gram (-) bacteremia.

Topics: Adolescent; Adult; Analysis of Variance; Bacteremia; Biomarkers; C-Reactive Protein; Child; Child, Preschool; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Infant; Interleukin-10; Interleukin-6; Interleukin-8; Male; Neoplasms; Neutropenia; Statistics, Nonparametric

The immunostimulatory activity of viridans streptococcal strains isolated from neutropenic patients with severe sepsis (n=9) or uncomplicated bacteraemia (n=10) was compared. Peripheral blood mononuclear cells from healthy individuals were stimulated with heat-killed bacteria or culture supernatants, and cytokine production assessed. All strains were potent inducers of IL1beta, IL8, and TNFalpha production. Heat-killed bacteria induced consistently higher IL1beta and TNFalpha production than did the cell-free bacterial supernatants (P<0.01). The strains did not induce any proliferative response, nor any significant TNFbeta or IFNgamma production. No difference in cytokine-inducing capacity could be detected between the cohorts of severe and nonsevere isolates. Comparison of strains causing severe and nonsevere episodes in the same patient (n=2) revealed a significantly higher induction of IL1beta by the severe episodes associated isolates as compared to the nonsevere (P<0.04). The study underscores the importance of the host-pathogen interplay in determining the level of inflammation, and hence the severity of disease.

Topics: Bacteremia; Cells, Cultured; Cytokines; Humans; Inflammation; Interleukin-1; Interleukin-8; Leukocytes, Mononuclear; Neutropenia; Sepsis; Tumor Necrosis Factor-alpha; Viridans Streptococci

The aim of the study was to evaluate the ability of procalcitonin, C-reactive protein, serum amyloid A, interleukin-6 and interleukin-8 to predict bacteraemia during the 2 first d of fever in neutropenic patients. A total of 94 febrile neutropenic episodes in 60 patients were studied. Plasma samples were analysed at 10-h intervals from the onset of fever. Clinical events were categorized into 4 groups: 1) bacteraemia caused by other agents than coagulase-negative staphylococci (non-CNS bacteraemia) (n = 21), 2) coagulase-negative staphylococci bacteraemia (n = 15), 3) microbiologically or clinically documented infection without bacteraemia (n = 26) and 4) fever of unknown origin (n = 32). In non-CNS bacteraemia all markers, except for serum amyloid A, showed significantly higher levels compared to patients with fever of unknown origin (p < 0.05). For non-CNS bacteraemia the highest negative predictive value was found for procalcitonin (94%), followed by interleukin-6 (89%), C-reactive protein (88%) and interleukin-8 (87%). Procalcitonin, with a cut-off level of 1.4 ng/ml during 10-20 h after fever onset, showed the highest positive predictive value (67%) for a non-CNS bacteraemia. In conclusion, the value of the analysed markers to predict a non-CNS bacteraemia in neutropenic patients was limited due to low sensitivity and positive predictive value. However, procalcitonin, interleukin-6, C-reactive protein, and interleukin-8 could give useful information for the clinician in excluding a non-CNS bacteraemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amyloid; Analysis of Variance; Antineoplastic Agents; Bacteremia; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Fever; Hematologic Neoplasms; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; Neutropenia; Probability; Prognosis; Protein Precursors; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric

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

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

This study was conducted on thirty-seven neonates and healthy neonates (sixteen full term and fourteen preterm). The study aimed at revealing the role played by the NK cells in neonatal sepsis and evaluating the sensitivity of NK cell number and cytotoxicity as diagnostic markers in infants with suspected early neonatal sepsis compared with the circulating cytokine IL-8 and CRP levels. All samples of peripheral blood lymphocytes were subjected to determination of CD16 and CD56 positive cells using flow cytometry and NK cytotoxicity using the standard 4h 51Cr release assay. Sera were separated to measure IL-8 using ELISA. Determination of CRP, using turbdimetric assay, as well as blood cultures were done for patient's group only. Out of the 37 cases of suspected early neonatal sepsis, 16 were given final diagnosis of sepsis. Seven infants (43.8%) in the sepsis group had culture-proven diagnosis, one of which had meningitis. The median CRP value was significantly higher in sepsis group (88 mg/L; range: 17-159 mg/L) compared with that in non-septic group (15.4 mg/L; range: 7.6-23.2 mg/L, p < 0.001) only 12-60 h after admission. On the other hand, newborns in the sepsis group had significantly higher serum levels of IL-8 (median 310 pg/mL; range: 37-583 pg/ml) at study entry than that in the non septic group (median 63 pg/mL; range: 32-94 pg/ml, P < 0.001). On admission, the NK activity, rather than the number of CD16 and CD56 positive cells was much affected where NK cytotoxicity was significantly lower in sepsis group (3.4 +/- 2.1%, range 0.9-7%) than that of the nonseptic group (18.3 +/- 6.7%: range 10.7- 25.3%, p < 0.01) and healthy neonates (23.8 +/- 4.7%: range 12.2-32.3%, p < 0.001). We may conclude that defective NK cell activity rather than NK cell number plays an important role in susceptibility to early onset neonatal sepsis. Evaluation of NK cytotoxicity as a marker in early diagnosis of neonatal sepsis reveals that the sensitivity, specificity and predictive values of reduced NK cytotoxicity (10% killing) was higher than both of CRP and IL-8, either individually or in combination. Additionally, reduced NK cytotoxicity showed high correlation with the severity and outcome of neonatal sepsis. Our data raise the possibility that the addition of NK cell activity to the standard work-up of critically ill patients with suspected sepsis could increase diagnostic certainty and generate an improved patient management.

Topics: Bacteremia; Biomarkers; C-Reactive Protein; CD56 Antigen; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Female; Flow Cytometry; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Interleukin-8; Killer Cells, Natural; Leukocyte Count; Male; Neutropenia; Predictive Value of Tests; Receptors, IgG; Sensitivity and Specificity; Sepsis

Serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor (TNF)-alpha were frequently measured during the first 30 days after allogeneic bone marrow transplantation (BMT) in 84 consecutive adult patients. Major transplant-related complications (MTCs) occurred in 33% of cases and included veno-occlusive liver disease, idiopathic pneumonia syndrome, severe endothelial leakage syndrome and >grade II acute graft-versus-host disease. Compared with patients having minor complications, those with MTCs developed higher levels at times of maximal clinical signs (all cytokines, P<0.001), between days 0-5 post-BMT (IL-6 and IL-8, P<0.05) and days 6-10 (L-6, P<0.001; IL-8 and TNF, P<0.01) post-BMT. We could not discriminate patterns of cytokine release that were specific for any subtype of MTC. Higher levels of IL-8 during days 0-5 were associated (P=0.044) with early (<40 days) death. Multivariate analysis including patient and transplant characteristics as well as post-BMT levels of C-reactive protein showed that high average levels of one or more of the cytokines within the first 10 days post-BMT were independently associated with MTC (Odd's ratio: 2.3 [1.2-4.5], P=0.011). This study shows that systemic release of proinflammatory cytokines contributes to the development of MTC and provides a rationale for pre-emptive anti-inflammatory treatment in selected patients.

Topics: Adult; Bacteremia; Bone Marrow Transplantation; C-Reactive Protein; Capillary Leak Syndrome; Female; Graft vs Host Disease; Hepatic Veno-Occlusive Disease; Humans; Interleukin-6; Interleukin-8; Leukemia; Male; Neural Tube Defects; Pneumonia; Risk Factors; Transplantation Conditioning; Transplantation, Homologous; Tumor Necrosis Factor-alpha

In a prospective observational study of 133 neutropenic episodes, interleukin (IL)-8 serum levels > 2000 pg/mL at the onset of fever had a sensitivity of 53% and a specificity of 97% as a predictor of gram-negative bacteremia (GNB; positive predictive value, 73%; negative predictive value, 94%). The rates of early death differed significantly between patients with high and those with low IL-8 levels (3/11 vs. 1/122; P< .01). Serum IL-8 levels at the onset of fever define a low-risk subgroup of patients who can safely be treated with monotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Cefepime; Cephalosporins; Drug Therapy, Combination; Fever; Gentamicins; Gram-Negative Bacterial Infections; Humans; Interleukin-8; Leukemia; Lymphoma; Male; Middle Aged; Netilmicin; Neutropenia; Predictive Value of Tests; Prospective Studies

Fever without localising signs in very young children remains a diagnostic problem. Until present, a clinical scoring system combined with leucocyte count, urine analysis and determination of CRP are recognised as being helpful to identify patients at risk of serious bacterial illness. In this study we asked the question whether the determination of procalcitonin (PCT), interleukin (IL)-6, IL-8 and interleukin-1 receptor antagonist (IL- Ra) was superior to these commonly used markers for the prediction of a serious bacterial infection (SBI). Children, 7 days to 36 months of age, with a rectal temperature above 38 degrees C and without localising signs of infection were prospectively enrolled. For each infant, we performed a physical examination, a clinical score according to McCarthy, a complete white cell count, an urine analysis and a determination of CRP. We further determined PCT, IL-6, IL-8, and IL-1Ra concentrations and compared their predictive value with those of the usual management of fever without localising signs. Each infant at risk of SBI had blood culture, urine and cerebrospinal fluid cultures when indicated, and received antibiotics until culture results were available. A total of 124 children were included of whom 28 (23%) had SBI. Concentrations of PCT, CRP and IL-6 were significantly higher in the group of children with SBI but IL-8 and IL-1Ra were comparable between both groups. PCT showed a sensitivity of 93% and a specificity of 78% for detection of SBI and CRP had a sensitivity of 89% and a specificity of 75%.. Compared to commonly used screening methods such as the McCarthy score, leucocyte count and other inflammatory markers such as interleukin-6, interleukin-8 and interleukin- receptor antagonist, procalcitonin and C-reactive protein offer a better sensitivity and specificity in predicting serious bacterial infection in children with fever without localising signs.

Topics: Bacteremia; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant; Infant, Newborn; Interleukin-1; Interleukin-6; Interleukin-8; Interleukins; Logistic Models; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Severity of Illness Index

The Yucatan micropig has been used to develop an experimental model of chronic bacteremia. This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man. Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria. During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters. A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease. In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate. In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8. At day five, all animals are alive, and five micropigs have positive blood cultures. This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.

Topics: Acute Kidney Injury; Acute-Phase Reaction; Animals; Anorexia; Ataxia; Bacteremia; Chronic Disease; Disease Progression; Escherichia coli Infections; Fever; Hematologic Diseases; Interleukin-6; Interleukin-8; Models, Animal; Multiple Organ Failure; Nephritis, Interstitial; Reproducibility of Results; Swine, Miniature; Systemic Inflammatory Response Syndrome

The diagnostic utility of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-8 (IL-8) were studied in 66 cancer patients with suspected infection (39 with definite foci of infection, 17 with antibiotic responses without foci and 10 with neoplastic fever without infection) and 26 patients scheduled for chemotherapy. The infection group (n=56) had higher median CRP (91 versus 19 mg/l, P<0. 001), PCT (0.28 versus 0.12 ng/ml, P<0.001) and IL-8 values (27.7 versus 16.9 pg/ml, P=0.032) than the non-infection group (n=36). In patients with suspected infection, only PCT was a good marker to discriminate bacteraemia with an area under the receiver operating characteristics curve of 0.92 (95% confidence interval (CI), 0.77-1. 0), but even PCT was less well able to differentiate between non-bacteraemic infections and neoplastic fever (0.56; 95% CI, 0. 35-0.77). In conclusion, PCT was a good indicator for bacteraemia, but none of the three markers were reliable indicators for minor infections in non-neutropenic cancer patients.

Topics: Bacteremia; Bacterial Infections; Biomarkers, Tumor; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-8; Male; Middle Aged; Neoplasm Staging; Neoplasms; Prospective Studies; Protein Precursors

The relationship between cytokines and sepsis has been studied frequently in the intensive care unit (ICU). However, the determination of cytokines in patients as they enter the emergency department (ED) would be more meaningful in predicting the outcome of infection. This study investigated plasma interleukin-8 in the ED as the predictor of bacteremia and sepsis. One hundred patients admitted through the ED with signs of systemic inflammatory response syndrome were studied. Plasma IL-8, IL-6, and tumor necrosis factor (TNF) were assayed by enzyme-linked immunosorbent assay. Patient's data were evaluated using the APACHE II scoring system as predictive factors of morbidity and mortality. Plasma IL-8 (149 pg/mL) detected bacteremia with a positive predictive value of 90.9% and a specificity of 98.7%. Results indicated that the odds ratios (ORs) of bacteremia were 24.78 (P < 0.01, CI = 2.27-270.8), 5.42 (P < 0.05, CI = 1.37-21.4), and 6.05 (P < 0.05, CI = 1.36-26.8) for IL-8, IL-6, and APACHE II, respectively. Occurrence of bacteremia was highly correlated with increases in plasma IL-8 (P < 0.01). IL-8 (OR = 8.25, CI = 1.03-65.9) and APACHE II scores (OR = 12.6, CI = 2.24-70.4) were found to be significantly better predictive factors of mortality (P < 0.01) than IL-6 (OR = 3.60, CI = 0.57-22.7), TNF (OR = 0.24, CI = 0.01-11.0) and age (OR = 1.02, CI = 0.98-1.06). During bacteremia, IL-8 also correlated well with patient use of a ventilator (P < 0.01, OR = 2.43, CI = 2.41-311.19), use of vasopressors (P < 0.05, OR = 2.67, CI = 1.79-370.78), length of stay in the hospital (P < 0.01, OR = 3.14, CI = 1.87-988.31), and stay in the ICU (P < 0.01, OR = 2.51, CI = 2.98-449.80). Measuring IL-8 on patients in the ED with apparent bacterial infections appears to be a reliable predictor of bacteremia and the severity of disease.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Bacteremia; Biomarkers; China; Emergencies; Emergency Service, Hospital; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Hospitals, University; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Odds Ratio; Predictive Value of Tests; Prospective Studies; Treatment Outcome

Bacterial sepsis is characterized by a systemic inflammatory state, with activation of numerous cell types. Phagocytes participate in this phenomenon by secreting various proinflammatory cytokines and enzymes. Matrix metalloproteinases (MMPs) such as gelatinases are produced by phagocytes and are thought to play an important role in processes of cell transmigration and tissue remodeling. In this work, we show that endotoxin (lipopolysaccharide [LPS]) and other inflammatory mediators, such as tumor necrosis factor (TNF), interleukin-8, and granulocyte colony-stimulating factor, induce a rapid (within 20 min) release of gelatinase-B (MMP-9) zymogen in whole human blood, as determined by gelatin zymography. The polymorphonuclear neutrophil was identified as the cell responsible for this rapid secretion, as a result of the release of preformed enzymes stored in granules. Normal human subjects given LPS intravenously showed a similar pattern of proMMP-9 secretion, with maximum plasma levels reached 1.5 to 3 h after LPS administration (P = 0.0009). Prior administration of TNF receptor:Fc, a potent TNF antagonist, to subjects given LPS, only partially blunted the release of proMMP-9 (P = 0.033). Ibuprofen, a cyclooxygenase inhibitor, did not alter this pattern of release. Increased levels of proMMP-9 and proMMP-2, as well as activated forms of MMP-9, were found in plasma from two patients with gram-negative sepsis. The levels of MMPs paralleled the severity of clinical condition and a marker of the severity of sepsis, plasma procalcitonin. These data indicate that MMPs are released in whole blood in response to various inflammatory mediators and that they could serve as sensitive and early markers for cell activation during the course of bacterial sepsis.

Topics: Aged; Bacteremia; Endotoxemia; Enzyme Precursors; Female; Gelatinases; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Humans; Inflammation Mediators; Interleukin-8; Lipopolysaccharides; Male; Metalloendopeptidases; Neutrophils; Tumor Necrosis Factor-alpha

We assessed the predictive value of procalcitonin (PCT) serum levels in neutropenic patients with fever and various types of infection, using a prospective 3 times weekly blood sampling protocol during 103 patient episodes. Compared with pre-fever levels, median PCT levels increased after fever onset from 0.16 ng/ml (day -1) to 0.34 ng/ml (day +1). In samples obtained within 32 h after fever onset, PCT levels differed significantly between (clinically or microbiologically) documented infection and unexplained fever (median 0.51 vs. 0.26 ng/ml), between bacteraemia and non-bacteraemic infection (median 0.8 vs. 0.27 ng/ml) and between Gram-negative bacteraemia and all other episodes (median 1.28 vs. 0.31 ng/ml). Receiver-operating-characteristic (ROC) curves indicated that the discriminatory power of PCT was best for predicting bacteraemia vs. non-bacteraemic infection (sensitivity 73%; specificity 86%; area under the ROC curve 0.795; cut-off value 0.5 ng/ml). Compared with interleukin-8 (IL-8) serum levels, test characteristics were similar in the prediction of bacteraemia vs. non-bacteraemic infection and in the prediction of documented infection vs. unexplained fever, while IL-8 was better than PCT in the prediction of Gram-negative bacteraemia (area under the ROC curve 0.965 vs. 0.758).

Topics: Adolescent; Adult; Aged; Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Fever of Unknown Origin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Interleukin-8; Middle Aged; Neutropenia; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sensitivity and Specificity

Circulating levels of interleukin (IL)-6, IL-8, soluble Fc gamma receptor type III (sFc gammaRIII), mannose-binding protein (MBP), and C-reactive protein (CrP) were assessed among febrile children with cancer and neutropenia. Levels of IL-6, IL-8, sFc gammaRIII, MBP, and CrP were measured in serum from 56 pediatric cancer patients at the time of admission for 121 episodes of febrile neutropenia (88 febrile episodes without identifiable source, 5 clinically documented infections, 20 episodes of bacteremia due to gram-positive and 5 due to gram-negative organisms, and 3 fungal infections). IL-6 and IL-8 levels were higher in patients with either bacteremia due to gram-negative organisms or fungal infections than in patients with febrile episodes without an identifiable source (P < .00001 for each). IL-6 and IL-8 levels were higher in children with bacteremia due to gram-negative organisms than in those with bacteremia due to gram-positive organisms (P = .0011 and P = .0003, respectively). The measured levels of CrP, MBP, and sFc gammaRIII were not useful for identifying the type of infection. These preliminary results show the potential usefulness of IL-6 and IL-8 as early indicators for life-threatening infections in febrile cancer patients with neutropenia.

Topics: Adolescent; Adult; Bacteremia; C-Reactive Protein; Carrier Proteins; Child; Collectins; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Infant; Interleukin-6; Interleukin-8; Male; Neoplasms; Neutropenia; Receptors, IgG; Retrospective Studies; Solubility

The aim of this prospective study was to evaluate if patients with endocarditis display a more extensive endothelial activation than those with bacteraemia but without endocarditis. Sixty-five patients with blood culture-verified Staphylococcus aureus bacteraemia were included and serum samples collected on admission were analysed by enzyme immunoassays. Elevated serum concentrations of adhesion molecules were found in most of the patients with S. aureus bacteraemia. Patients with endocarditis (n = 15) showed significantly higher serum E-selectin (median 156 ng/ml) and VCAM-1 (median 1745 ng/ml) concentrations compared with those with S. aureus bacteraemia but without endocarditis (80 ng/ml and 1172 ng/ml, respectively; P = 0.01 and P = 0.003). No significant difference was found between the groups concerning ICAM-1 (median 451 ng/ml versus 522 ng/ml). In addition, serum tumour necrosis factor-alpha (TNF-alpha) concentrations were significantly correlated (P < 0.002) to serum levels of E-selectin, ICAM-1 and VCAM-1.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Child; E-Selectin; Endocarditis; Female; Granulocyte Colony-Stimulating Factor; Humans; Intercellular Adhesion Molecule-1; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Prospective Studies; Staphylococcal Infections; Staphylococcus aureus; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

The impact of antibiotics on total endotoxemia and circulating tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 in 18 patients with severe bacteremic sepsis or septic shock due to gram-negative species was investigated. Endotoxemia, TNF-alpha, IL-6, and IL-8 were assayed before (H0) and 1 h (H1) and 4 h (H4) after the first antibiotic infusion. Endotoxemia decreased from H0 (median, 0.4 EU/mL; interquartile interval, 0.09-1.23) to H1 (median, 0.19 EU/mL; interquartile interval, 0.07-0.75; P = .03) and remained stable between H1 and H4 (median, 0.12 EU/mL; interquartile interval, 0.09-0.30; P = .4). IL-6 levels fell between H0 and H4 (P = .01) and between H1 and H4 (P = .03). IL-8 was higher at H0 than at H1 (P = .04) and at H4 (P = .01). These results suggest that endotoxemia is not increased by antibiotherapy of severe gram-negative bacteremia.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Drug Therapy, Combination; Endotoxins; Female; Gram-Negative Bacterial Infections; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Shock, Septic; Tumor Necrosis Factor-alpha

This study investigated whether cytokines and colony-stimulating factors can predict prognosis in patients with postoperative multiple organ failure (MOF). We evaluated 14 patients with postoperative MOF who underwent operation for cardiovascular disease. Seven patients recovered from MOF (survivors) and seven did not recover and died (nonsurvivors). The white blood cell (WBC) count, granulocyte colony-stimulating factor, monocytic colony-stimulating factor, interleukin-6 (IL-6), and IL-8 were measured on the day the patients were judged to be in MOF and each week thereafter until the patients recovered or died. Survivors and nonsurvivors were equivalent in terms of age, gender, proportion of use of extracorporeal circulation, operation time, volume of blood transfusion, time from operation to the onset of MOF, the MOF score, proportion of bacteremia, duration of MOF, and number of failed organs. The mean duration of MOF was less than 2 weeks in both groups; therefore the measurements were compared on the first day of MOF and 1 week later. No significant differences between the two groups in terms of WBC counts, colony-stimulating factors, and IL-6 levels were noted. However, the serum level of IL-8 was significantly higher in nonsurvivors than in survivors. Patients with a high serum levels of IL-8 at the time of MOF had a poor prognosis.

Topics: Aged; Aged, 80 and over; Bacteremia; Blood Transfusion; Cause of Death; Extracorporeal Circulation; Female; Follow-Up Studies; Forecasting; Granulocyte Colony-Stimulating Factor; Heart Diseases; Humans; Interleukin-6; Interleukin-8; Leukocyte Count; Macrophage Colony-Stimulating Factor; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Prognosis; Survival Rate; Time Factors

Bacterial sepsis is still a leading cause of neonatal morbidity and mortality. Early onset sepsis in particular, presents with a different clinical course and involves other pathogens than sepsis later in life. In this study, plasma concentrations and mRNA expression of granulocyte colony-stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, IL-8, and soluble intercellular adhesion molecule-1 (sICAM-1) of neonates with early onset sepsis were evaluated in cord blood and during the first days of life. Irrespective of prematurity, plasma levels of G-CSF, TNF-alpha, IL-1beta, IL-6, and IL-8, but not sICAM-1, were excessively elevated in septic neonates when compared with both healthy infants and infants with clinically suspected but not confirmed sepsis. Compared with the corresponding maternal levels, neonatal cytokine cord plasma levels were likewise highly elevated, indicating the endogenous cytokine production by the neonate. With the exception of TNF-alpha, mRNA expression in blood cells from septic infants was, however, not more frequently detectable than in those from nonseptic patients. Cytokine levels decreased significantly within the first days of life, whereas levels of sICAM-1 and C-reactive protein increased during the same time period. In summary, in contrast to C-reactive protein and sICAM-1, cord blood plasma levels, but not the presence of mRNA, of G-CSF, TNF-alpha, IL-1beta, IL-6, and IL-8 can predict neonatal early onset sepsis with a high sensitivity and specificity. Cell types other than blood cells are likely to contribute considerably to the high cytokine production in septic newborns.

Topics: Bacteremia; Blood Cells; Female; Fetal Blood; Gene Expression Regulation, Developmental; Germany; Granulocyte Colony-Stimulating Factor; Humans; Infant, Newborn; Infant, Premature; Interleukin-1; Interleukin-6; Interleukin-8; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications; Reference Values; RNA, Messenger; Transcription, Genetic; Tumor Necrosis Factor-alpha

We investigated the cytokine profile and peak levels of interleukin (IL) -6, IL-8, IL-10 and tumour necrosis factor (TNF) -alpha levels in 42 patients after allogeneic bone marrow transplantation (BMT). Eleven of them developed veno-occlusive disease (VOD) of the liver. Fourteen patients had moderate-to-severe acute graft-versus-host disease (aGvHD), 10 isolated bacteraemia and 7 had no major complication. Those who developed severe VOD (n=6) showed a short, very high IL-8 peak (median: 6632 pg/ml, range: 5546-10,000 vs. 280 pg/ml, 0-2042 in controls, p<0.01) 1-4 d after diagnosis of the liver disease. Five of these patients had high peak levels of IL-6. Five patients with mild VOD showed a lower increase in the cytokines tested. Bilirubin levels, at day of IL-8 peak, did not differ statistically between mild and severe VOD. The highest levels of IL-10 were found in those with aGvHD. IL-8 levels were also increased, but not to the same extent as in patients with severe VOD (p=0.01 vs. VOD). In patients with bacteraemia, very high levels of IL-6 were seen. In patients without major complications, the levels of cytokines were low. In conclusion, high levels of IL-8 occurred in severe VOD of the liver, which may be of value to determine prognosis.

Topics: Adolescent; Adult; Bacteremia; Biomarkers; Bone Marrow Transplantation; Child; Female; Graft vs Host Disease; Hepatic Veno-Occlusive Disease; Humans; Interleukin-6; Interleukin-8; Male; Prognosis; Transplantation, Homologous

Interleukin (IL)-12 is thought to be a key factor for the induction of interferon gamma (IFN-gamma), a cytokine essential for the lethal effects of endotoxin. We report here on the release of the nonfunctional subunit of IL-12, p40, as well as biologically active heterodimeric IL-12, p70, after administration of a lethal (n = 5) or sublethal (n = 8) dose of live Escherichia coli to baboons. Remarkably, on lethal challenge, peak levels of p40 were observed at 3 hours that were about twofold lower than those elicited after sublethal challenge (2,813 +/- 515 pg/mL v 4,972 +/- 732 pg/mL, P < .05). This disparity was also observed, although to a lesser extent, for IL-12 p70 antigen, of which maximum levels of 91 +/- 47 pg/mL and 151 +/- 41 pg/mL were measured 6 hours after a lethal or sublethal dose of E coli, respectively. Circulating p70 antigen correlated with IL-12 biologic activity (r = 0.869; P < .001). When comparing lethal to sublethal conditions, lower peak levels of IL-12 on lethal E coli sharply contrasted with higher levels of other proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, IL-1beta, IL-6, and IL-8 observed in these animals. Lower IL-12 concentrations in the lethal group may have resulted in part from the enhanced production of IL-10, a known inhibitor of IL-12 synthesis in vitro, as peak levels of this cytokine 3 hours postchallenge inversely correlated with peak levels of IL-12, in particular p40 (r = -0.802; P < .01). Contrary to what might be expected if IFN-gamma were solely induced by IL-12, lethally challenged baboons generated threefold more IFN-gamma at 6 hours than those receiving a sublethal dose (P < .05). Moreover, higher levels of IFN-gamma were associated with lower p40/p70 ratios, suggesting that, in agreement with observations in vitro, IFN-gamma may have preferentially upregulated the release of p70 over p40. These data show that IL-12 is released in experimental septic shock in nonhuman primates and suggest that IL-10 and IFN-gamma are involved in the regulation of this release. Furthermore, this study indicates that the systemic release of IL-12 might be essential, but is not likely sufficient, to promote lethal production of IFN-gamma in sepsis.

Topics: Animals; Bacteremia; Cytokines; Escherichia coli Infections; Gene Expression Regulation; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-8; Killer Cells, Natural; Papio; Phagocytes; Shock, Septic; T-Lymphocytes; Tumor Necrosis Factor-alpha

Using a monoclonal antibody enzyme immunoassay, the concentration of interleukin-8 (IL-8) in cerebrospinal fluid (CSF) from 52 patients suspected of having meningitis was studied. The CSF IL-8 concentration was significantly higher in septic meningitis of known and unknown etiology than in aseptic meningitis and significantly higher in aseptic meningitis than in patients without meningitis. The CSF levels of IL-8 correlated with the levels of tumor necrosis factor-alpha, leukocyte count, neutrophil count, protein level, CSF/blood glucose ratio, and the number of days patients were hospitalized. The IL-8 values used to distinguish septic from aseptic meningitis, at a cut-off point of 3.00 micrograms/l, showed a sensitivity of 81%, a specificity of 92%, and a positive predictive value of 96%. The results suggest that determining IL-8 levels may be useful in the differential diagnosis of meningitis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Interleukin-8; Male; Meningitis, Aseptic; Meningitis, Bacterial; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity; Tumor Necrosis Factor-alpha

Cytokines play a major role in the pathophysiology of sepsis and septic shock. Using enzyme immunoassays the acute serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), granulocyte-colony stimulating factor (G-CSF), interleukin-8 (IL-8), and leukemia inhibitory factor (LIF) were investigated in 90 patients with positive blood cultures and clinical signs of infection. In 27 patients samples were obtained on admission, after 1, 4, 12, 18, and 24 h, and then daily. The acute serum levels of IL-6, TNF-alpha, G-CSF, and IL-8 were significantly higher among patients with severe sepsis. Patients with Gram-negative infection had significantly higher levels of TNF-alpha on admission than did patients with Gram-positive infections (p = 0.0008). The levels of IL-6, G-CSF and, to some extent, TNF-alpha decreased rapidly in survivors within the first 24 h of admission to hospital and institution of treatment. LIF was detected in 8/90 in both survivors and nonsurvivors.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Cytokines; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Granulocyte Colony-Stimulating Factor; Growth Inhibitors; Humans; Interleukin-6; Interleukin-8; Leukemia Inhibitory Factor; Lymphokines; Male; Middle Aged; Prognosis; Tumor Necrosis Factor-alpha

Tumor necrosis factor (TNF) and interleukin (IL)-1 are two cytokines for which naturally occurring inhibitors have been identified. The present study was undertaken to evaluate the extent to which scavenging of TNF in bacteremia attenuates the plasma levels of IL-1 receptor antagonist (IL-1ra) and soluble TNF receptors (sTNFR). Ten male baboons received 2 x 10(9) colony-forming units/kg live Escherichia coli over 2 h and were subjected to either placebo or anti-TNF antibody (anti-TNF Ab) treatment (1 mg/kg CDP571, Celltech, UK) 2 h before E. coli infusion (observation time: 72h). IL-1ra (range: 50-100 ng/ml) and sTNFR (range: 55kDa, 20-25 ng/ml; 75 kDa, 30-35 ng/ml) release was more sustained than that of IL-1 and TNF and was significantly attenuated by anti-TNF treatment, as were the circulating levels of IL-1, IL-8, and monocyte chemotactic peptide-1 (MCP-1) in the anti-TNF Ab group. We conclude that the increase in circulating natural cytokine modulators observed in nonhuman primate bacteremia is under the partial control of endogenous TNF because it was influenced by anti-TNF pretreatment. This attenuation is comparable to the anti-TNF effect on the chemokine MCP-1.

Topics: Animals; Antibodies, Monoclonal; Bacteremia; Chemokine CCL2; Escherichia coli Infections; Interleukin-1; Interleukin-8; Male; Papio; Receptors, Interleukin-1; Receptors, Tumor Necrosis Factor; Solubility; Tumor Necrosis Factor-alpha

The chemokine monocyte chemotactic protein 1 (MCP-1) is a cytokine with chemotactic activity specific for mononuclear phagocytes. To investigate the possible involvement of MCP-1 in the pathogenesis of sepsis, its course was studied in baboons challenged intravenously with a sublethal or lethal dose of Escherichia coli. Levels of MCP-1 started to increase in both groups of animals 2 h after injection of E. coli, reaching peak levels 4 and 6 h after a sublethal (186 +/- 21 ng/mL) or a lethal (213 +/- 24 ng/mL) dose, respectively. Levels of MCP-1 correlated significantly with plasma levels of another chemokine, interleukin-8 (IL-8; r = .826. P < .001), suggesting that common stimuli mediate the release of both cytokines in this model.

Topics: Animals; Bacteremia; Chemokine CCL2; Chemotactic Factors; Cytokines; Escherichia coli Infections; Interleukin-8; Papio; Time Factors

The cause of allograft liver dysfunction after transplantation is unresolved. We tested the hypothesis that human donor liver may be predisposed to ischemia reperfusion injury, and graft dysfunction subsequent to ongoing inflammatory processes during donor hospitalization.. A prospective study of organ donors and transplant recipients of allograft livers from these donors was conducted. Portal venous, inferior vena caval, and superior vena caval blood samples were obtained from 16 clinical organ donors at the time of organ procurement (one to 12 days post-trauma) to characterize the hepatic cytokine and acute phase protein response, to determine whether or not this response resulted from bacterial or endotoxin translocation to the portal circulation, and to assess whether or not transplant outcome was associated with plasma levels of cytokines in the donor.. In comparison with systemic blood samples from ten healthy persons, all 16 donors exhibited significantly (p < 0.05) elevated plasma concentrations of interleukin-6, interleukin-8, soluble p55 tumor necrosis factor receptor type I (sTNFr-I), and C-reactive protein. No concentration differences existed among portal venous, inferior vena caval, and superior vena caval blood samples for any cytokine or acute phase protein measured. Donor levels of endotoxin, TNF-alpha, soluble intercellular adhesion molecule-1 (sICAM-1), alpha 1-acid glycoprotein, alpha 1-antitrypsin, and haptoglobin were comparable with those in the healthy persons. Bacterial cultures of portal blood were negative. There was no association between the causation of donor trauma and either donor cytokine response or function and quality of the allograft liver after transplantation. Nor could an association between donor cytokine response and either early allograft function (less than 96 hours) or eventual transplant outcome in the recipients be detected.. These results indicate that, although an ongoing inflammatory response to injury was evident in these donors at the time of organ procurement, there were no apparent adverse effects arising from these inflammatory processes on the function and quality of the donor liver after transplantation. Bacterial translocation does not seem to be a component of the pathogenesis of inflammation. Whether or not the presence of inflammation in the donor alters the metabolic responses of the allograft liver and recipient to transplant operation is unknown.

Topics: Acute-Phase Proteins; Adolescent; Adult; Bacteremia; C-Reactive Protein; Cytokines; Endotoxins; Female; Graft Survival; Humans; Interleukin-6; Interleukin-8; Liver; Liver Circulation; Liver Transplantation; Male; Middle Aged; Portal System; Prospective Studies; Receptors, Tumor Necrosis Factor; Tissue and Organ Procurement; Tissue Donors; Tissue Preservation; Transplantation, Homologous; Tumor Necrosis Factor-alpha

To elucidate the relationship between active oxygen and interleukin 8 (IL-8) in patients with septic adult respiratory distress syndrome (ARDS), we determined the serum levels of alpha-tocopherol, which has an antioxidant action, and IL-8 in seven patients with this disease. Serum alpha-tocopherol and IL-8 levels determined at the time of diagnosis of septic ARDS were 0.97 +/- 0.36 mg/dl and 0.98 +/- 0.99 ng/ml, respectively. A significant correlation was found between serum alpha-tocopherol level and IL-8 level (r = -0.758, p = 0.0473). These findings suggest that IL-8 activates neutrophils, which produce active oxygen.

Topics: Adolescent; Adult; Aged; Bacteremia; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Male; Middle Aged; Reactive Oxygen Species; Respiratory Distress Syndrome; Vitamin E

To evaluate the role of interleukin (IL)-8 in meningococcal disease, a solid-phase double-ligand ELISA was used to quantitate IL-8 in sera and cerebrospinal fluid (CSF) from patients with meningococcal meningitis, bacteremia, or both with or without septic shock. IL-8 was demonstrated in sera from 28 of 62 patients; levels were significantly higher in patients with septic shock without meningitis (median, 36.1 ng/mL) than in patients with other manifestations (median, < 0.02 ng/mL), and 4 of 5 patients who died had high levels. IL-8 was detected in all 27 CSF samples. Serum IL-8 levels correlated highly significantly with those of IL-6 (r = .83) and tumor necrosis factor (TNF; r = .64), while the correlations between corresponding CSF levels were less pronounced (r = .43 and r = .38, respectively) but still significant. Serum IL-8 levels were highest in patients with a symptom history < 12 h. The elimination rate of IL-8 from serum varied and was similar to that of IL-6 and TNF. IL-8 appears to participate in the complex cytokine network during the initial phase of systemic meningococcal infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Child; Child, Preschool; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Kinetics; Leukocyte Count; Male; Meningitis, Meningococcal; Meningococcal Infections; Middle Aged; Neutrophils; Shock, Septic; Tumor Necrosis Factor-alpha

Because of its neutrophil-activating properties, interleukin-8 (IL-8) may play an important role in the pathophysiology of sepsis. We measured circulating IL-8 levels in 47 patients with clinical sepsis. Levels on admission were elevated in 42 of the 47 patients (89%) and were comparable in patients with gram-positive or gram-negative infections. Patients with shock had significantly higher IL-8 levels than normotensive patients (P = 0.0014, Wilcoxon-Mann-Whitney test), whereas no differences in IL-8 levels were found between patients with or without adult respiratory distress syndrome. Patients who died had higher IL-8 levels on admission than the patients who survived. The largest differences in IL-8 levels between survivors and nonsurvivors was found when only patients with positive cultures were considered (P = 0.0342). IL-8 levels appeared to correlate significantly with lactate levels and inversely with leukocyte and platelet numbers and mean arterial pressure. In addition, the IL-8 level in the sepsis patients was found to correlate significantly with levels of IL-6, elastase-alpha 1-antitrypsin, and C3a. Serial observations revealed that in most patients IL-8 levels decreased, irrespective of the outcome. Thus, our results demonstrate that IL-8 levels are increased in most patients with sepsis and correlate with some important clinical, biochemical, and inflammatory parameters. These findings suggest a role for IL-8 in the pathophysiology of sepsis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin; Bacteremia; Blood Pressure; Complement C3a; Enzyme-Linked Immunosorbent Assay; Factor XII; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Interleukin-6; Interleukin-8; Lactates; Lactic Acid; Lactoferrin; Leukocyte Elastase; Middle Aged; Pancreatic Elastase; Prekallikrein; Respiratory Distress Syndrome; Shock, Septic