AJP - Regulatory, Integrative and Comparative Physiology, Vol 265, Issue 3 512-R517, Copyright © 1993 by American Physiological Society

ARTICLES

Role of hypothalamic interleukin-6 and tumor necrosis factor-alpha in LPS fever in rat

J. J. Klir, J. Roth, Z. Szelenyi, J. L. McClellan and M. J. Kluger
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.

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 lipopolysaccharide (LPS)-induced fever in rats. Additionally, slow anterior 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 collected 60 min before and 60, 180, 300, and 420 min after the intraperitoneal injection of LPS. A control group was injected intraperitoneally with saline. The core temperature (measured by biotelemetry) of LPS-injected rats was significantly higher (P < 0.05) than the temperature of the rats injected with saline at 180, 300, and 420 min after the injection. 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 levels of IL-1-like activity. Infusion of hrIL-6 at a level similar to the peak IL-6 level measured during LPS-induced fever resulted in a slowly developing and long-lasting increase in core temperature. Infusion of hrTNF at a level corresponding to the peak TNF level measured during LPS-induced fever did not induce a significant increase in core temperature. These results support the hypothesis that elevated hypothalamic concentrations of IL-6 are involved in the induction of fever elicited by peripheral (intraperitoneal) injection of LPS.

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