interleukin-8 and Meningococcal-Infections

Proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-6 and -8), counterinflammatory compounds (IL-10 and soluble TNF receptors p55 and p75 [sTNFR-55 and -75]), and hemostatic parameters were determined in 38 patients with meningococcal septic shock. Eleven patients (29%) died. Serum levels of pro- and counterinflammatory compounds and plasma levels of plasminogen activator inhibitor (PAI)-1 were significantly higher in nonsurvivors. The interval between appearance of petechiae and blood sampling was shorter in nonsurvivors than in survivors (3.6 +/- 2.4 vs. 6.1 +/- 3.3 h; P = 0.4). This interval correlated strongly with the levels of TNF-alpha, IL-6, -8, and -10, sTNFR-55 and -75, and PAI-1. However, with the exception of PAI-1, differences between concentrations of these mediators disappeared after adjustment for the interval. PAI-1 levels correlated with TNF-alpha concentrations (r = .75; P < .001) and were 1.9 (P = .01) times higher in nonsurvivors at a similar TNF-alpha concentration. Thus, an increased PAI-1 response to TNF-alpha may be associated with fatality, probably because of polymorphism of the PAI-1 gene.

Topics: Adolescent; Antigens, CD; Blood Coagulation; Child; Child, Preschool; Cytokines; Female; Fibrinolysis; Humans; Infant; Interleukin-10; Interleukin-6; Interleukin-8; Male; Meningococcal Infections; Plasminogen Activator Inhibitor 1; Prospective Studies; Purpura; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Shock, Septic; Tumor Necrosis Factor-alpha

The objective of this study was to establish a porcine analog of human meningococcal sepsis for pathophysiological investigations and possible future therapy in severe sepsis. Heat-killed Neisseria meningitidis was continuously infused in sublethal concentrations into 10 anesthetized 30-kg pigs (sepsis group). The dose was doubled every 30 min. Six pigs received saline only (control group). The changes described in the succeeding paragraphs were observed in the sepsis group but not in the control group. MAP was aimed to be kept normal by fluid infusion but declined after 3 h in parallel with a decrease in systemic vascular resistance. Pulmonary arterial pressure increased considerably after 30 to 45 min. A massive plasma extravasation was shown by increased hematocrit and a 50% reduction in plasma albumin content. Fluid accumulated in lungs, muscles, and jejunum, as shown by increased wet-dry ratios. Peak inspiratory pressures and fraction of inspired oxygen had to be increased. The cytokines TNF-alpha, IL-1beta, IL-6, IL-8, IL-10, and IL-12 increased markedly. Neutrophils fell to zero-levels, and platelets were markedly reduced. Thrombin-antithrombin complexes increased notably after 120 min. This is the first large animal model of sepsis using whole Neisseria meningitidis. The model simulates well central aspects of human meningococcal sepsis and could be used for future interventional studies.

Topics: Animals; Disease Models, Animal; Female; Interleukin-10; Interleukin-12; Interleukin-6; Interleukin-8; Male; Meningococcal Infections; Neisseria meningitidis; Random Allocation; Shock, Septic; Swine; Tumor Necrosis Factor-alpha

The aim of this study was to test the hypothesis that elevated lipopolysaccharide binding protein (LBP) serum concentration is a useful marker in the early diagnosis of invasive bacterial infection in children. We measured LBP in serum and cerebrospinal fluid (CSF) of children with proven invasive infection caused by Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis.. Samples were collected from 39 children (aged 2 months to 17 years) with bacterial sepsis (n = 19) or meningitis (n = 20). Bacterial infection was diagnosed when a blood or CSF culture was positive and clinical signs of invasive infection were present. The control group consisted of serum (n = 60) and CSF (n = 19) samples from children with neurologic disease, juvenile idiopathic arthritis or viral infection. In 10 patients with bacterial infection, follow-up samples (24 and 48 hours) were available. LBP values were measured by an immunochemiluminescence analyzer (IMMULITE; DPC Biermann, Bad Nauheim, Germany) and compared with tumor necrosis factor-alpha and interleukin-8 concentrations.. The median LBP serum concentrations in patients with bacterial infection were markedly elevated compared with the control groups (45.0 [33.1-55.2] versus 8.3 [6.8-10.1] microg/mL [median and 5-95% confidence interval]; P < 0.0001). Follow-up serum values of LBP were persistently elevated despite adequate antibiotic treatment, whereas tumor necrosis factor-alpha and interleukin-8 concentrations decreased. In contrast, LBP concentrations in the CSF were below the detection limit of 0.5 microg/mL in 67% of patients with bacterial meningitis (median <0.5 microg/mL), whereas tumor necrosis factor-alpha and interleukin-8 levels were highly elevated.. LBP serum concentration is elevated in serum of children with invasive bacterial infection and could be a promising diagnostic marker.

Topics: Acute-Phase Proteins; Adolescent; Biomarkers; Carrier Proteins; Cerebrospinal Fluid; Child; Child, Preschool; Haemophilus Infections; Haemophilus influenzae; Humans; Immunoassay; Infant; Interleukin-8; Luminescent Measurements; Membrane Glycoproteins; Meningitis, Bacterial; Meningococcal Infections; Neisseria meningitidis; Pneumococcal Infections; Sepsis; Serum; Streptococcus pneumoniae; Time Factors; Tumor Necrosis Factor-alpha

Meningococcal lipooligosaccharide (LOS) induces a strong proinflammatory response in humans during meningococcal infection. We analyzed the role of LOS in the inflammatory response and virulence during the early infectious process in a mouse model of meningococcal respiratory challenge. An lpxA mutant strain (serogroup B) devoid of LOS (strain Z0204) could not persist in the lungs and did not invade the blood. The persistence in the lungs and invasion of the bloodstream by a rfaD mutant expressing truncated LOS with only lipid A and 3-deoxy-d-manno-2-octulosonic acid molecules (strain Z0401) was intermediate between those of the wild-type and Z0204 strains. Both LOS mutants induced acute pneumonia with the presence of infiltrating polymorphonuclear leukocytes in lungs. Although tumor necrosis factor alpha production was reduced in mice infected with the mutant of devoid LOS, both LOS mutants induced production of other proinflammatory cytokines, such as interleukin-1beta (IL-1beta), IL-6, and the murine IL-8 homolog KC. Together, these results suggest that meningococcal LOS plays a role during the early infectious and invasive process, and they further confirm that other, nonlipopolysaccharide components of Neisseria meningitidis may significantly contribute to the inflammatory reaction of the host.

Topics: Animals; Chemokines; Cytokines; Female; Interleukin-1beta; Interleukin-6; Interleukin-8; Lipopolysaccharides; Lung; Meningococcal Infections; Mice; Mice, Inbred BALB C; Mutation; Neisseria meningitidis; Pneumonia, Bacterial; Respiratory Tract Infections; Virulence; Virulence Factors

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

Procalcitonin (PCT), a precursor of calcitonin, is a recognised marker of bacterial sepsis, and high concentrations correlate with the severity of sepsis. PCT has been proposed as an earlier and better diagnostic marker than C reactive protein (CRP) and white cell count (WCC). This comparison has never been reported in the differentiation of meningococcal disease (MCD) in children presenting with a fever and rash.. To determine if PCT might be a useful marker of MCD in children presenting with fever and rash.. PCT, CRP, and WCC were measured on admission in 108 children. Patients were classified into two groups: group I, children with a microbiologically confirmed clinical diagnosis of MCD (n = 64); group II, children with a self limiting illness (n = 44). Median ages were 3.57 (0.07-15.9) versus 1.75 (0.19-14.22) years respectively. Severity of disease in patients with MCD was assessed using the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS).. PCT and CRP values were significantly higher in group I than in group II (median 38.85 v 0.27 ng/ml and 68.35 v 9.25 mg/l; p < 0.0005), but there was no difference in WCC between groups. Sensitivity, specificity, and positive and negative predictive values were higher for PCT than CRP and WCC. In group I, procalcitonin was significantly higher in those with severe disease (GMSPS >/=8).. PCT is a more sensitive and specific predictor of MCD than CRP and WCC in children presenting with fever and a rash.

Topics: Adolescent; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Exanthema; Fever; Humans; Infant; Interleukin-6; Interleukin-8; Meningococcal Infections; Protein Precursors; Sensitivity and Specificity; Tumor Necrosis Factor-alpha

Myalgia is under-recognized in meningococcal disease (MCD). In septic shock, myositis is thought to be mediated by pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and interleukin-6 (IL-6) but this has never previously been studied in MCD. We aimed to demonstrate whether muscle damage mediated via TNF-alpha and other pro-inflammatory cytokines occurs in MCD, as estimated by creatine kinase skeletal muscle isoenzyme (CK-MM) and cardiac isoenzyme (CK-MB) concentrations.. A total of 68 children, median age 2.7 years, with a diagnosis of MCD were prospectively studied. Severity of disease was measured using the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS). Severe disease was defined as a GMSPS of > or =8. TNF-alpha, IL-8, IL-6 and IL-1Ra concentrations were determined on samples taken on admission.. CK-MM correlated significantly with TNF-alpha, IL-8 and GMSPS. There was no significant correlation between CK-MB and TNF-alpha or IL-6, but CK-MB correlated with GMSPS and IL-8. Fifty-six percent of children with MCD had evidence of muscle damage as manifested by elevated CK-MM.. TNF-alpha and IL-8 may be potential mediators in the pathophysiology of skeletal muscle damage in MCD.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Creatine Kinase; Creatine Kinase, MB Form; Creatine Kinase, MM Form; Female; Humans; Infant; Interleukin-8; Isoenzymes; Male; Meningococcal Infections; Myositis; Prospective Studies; Severity of Illness Index; Tumor Necrosis Factor-alpha

Because interleukin 8 (IL-8) is a potent neutrophil chemotactic and activating cytokine, we investigated IL-8 production in relation to neutrophil migration and elastase release in the human lung during unilateral community-acquired pneumonia (CAP). In 17 patients, the local response in the involved lung was compared with that in the contralateral, noninvolved lung, and with the systemic response. Eight healthy volunteers served as controls. IL-8, total neutrophil elastase (NE), free elastase activity, alpha 1-antitrypsin (alpha 1-AT), and total leukocyte and neutrophil counts were evaluated in bronchoalveolar lavage fluids (BALF). Mean IL-8 concentrations in BALF from the involved lungs of the patients were significantly greater than those in BALF from the noninvolved lung or from controls (p < or = 0.001). By contrast, the serum IL-8 concentration was not different in patients and in controls. Total NE and alpha 1-AT concentrations were increased in BALF from the involved lung as compared with the noninvolved lung or controls (p < or = 0.001). The elastase-inhibitory capacity of alpha 1-AT in BALF was impaired in the involved lung of seven of the 14 patients as compared with the controls, leading to free elastase activity in the involved lung of all patients with CAP. Plasma total NE concentrations were significantly greater in the CAP patients than in the controls. IL-8 concentrations in BALF correlated positively with total leukocyte counts, absolute numbers and percentages of neutrophils, total NE concentrations, and free elastase activity. Our results suggest that during unilateral CAP, locally produced IL-8 may trigger neutrophil accumulation and activation, thus contributing to a local elastase/antielastase imbalance within the site of infection.

Topics: Adolescent; Adult; Aged; Albumins; alpha 1-Antitrypsin; Bronchoalveolar Lavage Fluid; Community-Acquired Infections; Data Interpretation, Statistical; Female; Haemophilus Infections; Humans; Immunoenzyme Techniques; Interleukin-8; Leukocyte Count; Leukocyte Elastase; Lung; Male; Meningococcal Infections; Middle Aged; Neutrophils; Pancreatic Elastase; Pneumococcal Infections; Pneumonia, Bacterial

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