ROLE OF HYPOTHALAMIC INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR-ALPHA INLPS FEVER IN RAT

The purpose of this study was to determine, using push-pull perfusion, the levels of interleukin (IL)-1-like, IL-6-like, and tumor necrosis factor-alpha (TNF)-like activity in the anterior hypothalamus during l ipopolysaccharide (LPS)-induced fever in rats. Additionally, slow ante rior hypothalamic infusions of human recombinant IL-6 (hrIL-6) or TNF (hrTNF) for several hours were performed to determine possible febrile effects of these two cytokines. Artificial cerebrospinal fluid (aCSF) was infused as a control. Samples of cerebrospinal fluid were collect ed 60 min before and 60, 180, 300, and 420 min after the intraperitone al injection of LPS. A control group was injected intraperitoneally wi th saline. The core temperature (measured by biotelemetry) of LPS-inje cted rats was significantly higher (P < 0.05) than the temperature of the rats injected with saline at 180, 300, and 420 min after the injec tion. The average postinjection IL-6 levels were significantly higher (P < 0.05) in the LPS-injected group. TNF was significantly higher (P < 0.05) than the baseline only at 180 min. There were no changes in le vels of IL-1-like activity. Infusion of hrIL-6 at a level similar to t he peak IL-6 level measured during LPS-induced fever resulted in a slo wly developing and long-lasting increase in core temperature. Infusion of hrTNF at a level corresponding to the peak TNF level measured duri ng LPS-induced fever did not induce a significant increase in core tem perature. These results support the hypothesis that elevated hypothala mic concentrations of IL-6 are involved in the induction of fever elic ited by peripheral (intraperitoneal) injection of LPS.