The antiinflammatory mediators interleukin (IL)-10 and soluble tumor necrosis factor (TNF) receptors p55 (sTNFR-55) and sTNFR-75 in cerebrospinal fluid (CSF) from 37 children with bacterial meningitis were studied. CSF concentrations of IL-10, sTNFR-55, and sTNFR-75 and of the proinflammatory cytokines TNF-alpha, IL-6, and IL-8 were markedly elevated and were, with the exception of the sTNFRs, significantly higher in CSF than in serum. CSF concentrations of sTNFR- 55 and sTNFR-75 were only associated positively with IL-10 levels. CSF glucose levels correlated highly with levels of IL-10, sTNFR-55, and sTNFR-75 and weakly with TNF-alpha and IL-6. Cytokine levels in CSF decreased rapidly, while sTNFR levels remained elevated for at least 24 h.

Sepsis or septic shock is frequently associated with activation of the complement system, coagulation and fibrinolytic changes and the release of several cytokines. In this study we analyzed the relation of complement activation to the inflammatory mediators, hemodynamic and biochemical parameters and severity of illness and outcome in 20 consecutive patients with clinically defined sepsis. Levels of C3a and C3d were elevated in 90% of the patients (median levels 0.19 mg/l and 8.6 mg/l respectively) in comparison to 14% and 42%, respectively of 7 patients with non-septic shock. Levels of C4 were decreased in only 1 of the 20 septic patients. Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, respectively (median levels 122 ng/l and 1300 U/ml) and were clearly interrelated (r = 0.67, p less than 0.01). C3a levels correlated with the APACHE II score (r = 0.57, p less than 0.05) and high C3a levels were associated with fatal outcome (p less than 0.05). C3a was also correlated inversely with mean arterial pressure (r = 0.50, p less than 0.01). Levels of complement C3a and C3d significantly correlated with levels of plasminogen activator inhibitor-1 (PAI) and correlated inversely with AT-III levels. We found no correlation between these complement products and leukocyte counts or lactate levels, nor was there a correlation between C3a or C3d and the cytokines TNF and IL-6. Levels of C3a and C3d did not decrease significantly during the first 24 h of treatment, in contrast to a clear decrease in IL-6 levels in all patients and a decrease in TNF in the surviving patients. TNF levels remained stable or increased in the non-survivors. We conclude that both the complement system and the cytokine system are involved in the pathogenesis of septic shock and may be involved in the development of some of the fatal complications like hypotension and disseminated intravascular coagulation.

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