TNF AND IL-1 IN A RABBIT MODEL OF MENINGITIS

Tumor necrosis factor (TNF) and interleukin 1 (IL-1) have been implica ted in the pathogenesis of bacterial meningitis. We have used a rabbit model where meningitis was induced bu intracisternal injection of Esc herichia coli lipopolysaccharide (LPS) and the pathology was quantitat ed by the counts of leukocyes in the cerebrospinal fluid (CSF). In thi s model, injections of 200 ng of LPS induced a marked leukocyte infilt ration. LPS-treated rabbits also had high TNF levels (ng/ml) in the CS F. However, administration of even high doses of recombinant TNF (500 ng) had a less marked effect. Similarly, administration of IL-1 induce d a lower leukocyte infiltration and with a delayed effect. While IL-1 was not detectable in the CSF of LPS-treated rabbits, cotreatment wit h an IL-1 receptor antagonist (IL-1Ra) showed a trend for a protective effect, thus not excluding a role for IL-1. On the other hand, dexame thasone, a potent inhibitor of the synthesis of most cytokines, almost completely blocked LPS-induced leukocytosis. These data suggest that IL-1 and TNF are not the only cytokines implicated in the pathogenesis ot meningitis.