ROLE OF HYPOTHALAMIC INTERLEUKIN-1-BETA IN FEVER INDUCED BY CECAL LIGATION AND PUNCTURE IN RATS

Bacterial endotoxin induces fever by causing the release of interleuki n (IL)-1 beta into the circulation or the brain. IL-1 beta is believed to mediate fever via triggering the production and/or release of IL-6 in the hypothalamus. The present study examined whether IL-1 beta and IL-6 in the hypothalamus of the rat are also involved in fever during bacterial sepsis caused by cecal ligation and puncture (CLP). CLP ind uces fever for 2 days. Polyclonal rabbit antibody against rat IL-1 bet a (anti-IL-1 beta, 2 mu g/mu l) or control rabbit IgG (2 mu g/mu l) wa s unilaterally microinjected into the hypothalamus of rats immediately after or 24 h after CLP or sham-CLP surgery. Anti-IL-1 beta injected 24 h after CLP (when fever was already present) or sham-CLP surgery di d not affect fever. Microinjection of anti-IL-1 beta into the hypothal amus immediately after surgery caused a significant decrease in body t emperature during the night after CLP surgery and a 48% reduction of f ever on the following day. Although blood plasma levels of IL-6 were s ignificantly elevated 1.5, 6, 24, and 48 h after CLP surgery, there we re no differences in IL-6 concentrations in the extracellular fluid of the anterior hypothalamus (collected by push-pull perfusion). These d ata suggest that fever due to bacterial sepsis is initiated by IL-1 be ta within the hypothalamus, and this febrile response, unlike endotoxi n-induced fever, is not accompanied by elevation in the hypothalamic c oncentration of IL-6.