THE IMMUNOLOGY OF SEPSIS AND MENINGITIS - CYTOKINE BIOLOGY

Although antibiotics have reduced mortality, the most recent clinical trials in sepsis and meningitis have been directed at the host inflammatory response in an attempt to improve outcome. Endotoxin, cell wall constituents and toxins are potent inducers of small molecular weight proteins (cytokines) from a variety of host cells. Several lines of investigation have implicated tumor necrosis factor-alpha (TNF-alpha) as a cytokine mediator of sepsis and septic shock. A recent study has been able to measure plasma TNF-alpha concentrations in patients with meningococcemia and demonstrated a correlation with prognostic groups related to mortality. Therefore, TNF-alpha, probably through its effects on other mediators, has an effect in sepsis. New speculation regarding morbidity in bacterial meningitis focuses on cytokine activity in the central nervous system. Cerebrospinal fluid (CSF) from experimental animals with meningitis contains increased amounts of interleukin-1-beta-(IL-1-beta) and TNF-alpha. These IL-1-beta levels correlated directly with duration of fever and neurological sequelae. Children with Haemophilus influenzae, type b meningitis treated with dexamethasone had significantly reduced levels of CSF IL-1-beta compared to placebo-treated controls.