INHIBITION OF NITRIC-OXIDE SYNTHASE RESULTS IN A SUPPRESSION OF INTERLEUKIN-1-BETA-INDUCED FEVER IN RATS

Pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta) indu ce nitric oxide synthase. The purpose of this study was to investigate the role of endogenous nitric oxide in IL-1 beta-induced fever in rat s. At a dose of 2.5 mu g per animal intraperitoneal (i.p.) injections of rat recombinant IL-1 beta evoked a febrile response with a duration of 8 hours. Simultaneous i.p. injection of 50 mg/kg N-nitro-L-arginin e methyl ester hydrochloride (L-NAME) resulted in a complete suppressi on of IL-1 beta-induced fever in rats. I.p. injection of 50 mg/kg L-NA ME alone had no apparent influence on body core temperature. Endogenou s formation of IL-6 in response to IL-1 beta was not suppressed but ra ther enhanced by treatment with L-NAME during the early stage of IL1 b eta-induced fever. This result indicates that activation of nitric oxi de synthase and thereby endogenous NO-formation is essential for the g eneration of an IL-1 beta-induced febrile response in rats and that th e suppression of IL-1 beta-induced fever by treatment with L-NAME seem s not to be caused by an inhibition of IL-6 production. (C) 1998 Elsev ier Science Inc.