TUMOR-NECROSIS-FACTOR-ALPHA INDUCES ONLY MINOR INFLAMMATORY CHANGES IN THE CENTRAL-NERVOUS-SYSTEM, BUT AUGMENTS EXPERIMENTAL MENINGITIS

Although tumour necrosis factor alpha is said to play a key role in ba cterial meningitis and other CNS diseases, the effects of this pro-inf lammatory cytokine have only been studied in part and are incompletely understood. In a rat model, we investigated the effect of intracister nal injection of recombinant rat-specific tumour necrosis factor alpha (5, 35, 70 and 280 mu g tumour necrosis factor alpha) (i) alone, (ii) combined with pneumococcal cell wall components, on regional cerebral blood flow, intracranial pressure, white blood cell count in the cere brospinal fluid, and brain water content. Tumour necrosis factor alpha dose-dependently caused an increase in regional cerebral blood flow ( up to 221 +/- 43% of baseline values) over the six hour observation pe riod and mild cerebrospinal fluid leukocytosis; intracranial pressure and brain water content were unchanged. Hypothesizing that regional ce rebral blood flow changes are dependent on nitric oxide, tumour necros is factor alpha-induced regional cerebral blood flow increase was abol ished by Aminoguanidine, a selective inhibitor of inducible nitric oxi de synthase. Combination of the lowest tumour necrosis factor alpha do se and a low dose pneumococcal cell wall preparation magnified the inf lammatory effect of both. We conclude that intrathecally injected tumo ur necrosis factor alpha alone results in only minor inflammatory chan ges, whereas it dramatically augments experimental meningitis. (C) 199 8 IBRO. Published by Elsevier Science Ltd.