An interleukin-1 receptor fragment inhibits spontaneous sleep and muramyl dipeptide-induced sleep in rabbits.. Takahashi, Satoshi, Levente Kapas, Jidong Fang, Jerome M. Seyer, Ying Wang, and James M. Krueger. Departments of Physiology and Biophysics, and Biochemistry, University of Tennessee, Memphis, TN 38163
APStracts 3:0023R, 1996.
Interleukin-1 (IL-1) is hypothesized to be involved in physiological sleep regulation and in sleep responses occurring during infectious disease. If this hypothesis is correct, then inhibition of endogenous IL-1 should reduce both normal sleep and muramyl dipeptide (MDP) -induced sleep. MDP is a somnogenic substance derived from bacterial cell walls. We report here the effects of a synthetic IL-1 receptor fragment corresponding to amino acid residues 86-95 of the human type I IL-1 receptor [IL-1RF] on spontaneous sleep and IL-1[beta]- and MDP-induced sleep and fever in rabbits. Two doses of the IL-1RF (25 [mu]g and 50 [mu]g) were injected into normal rabbits intracerebroventricularly (icv). Both doses significantly decreased spontaneous non-rapid-eye-movement sleep (NREMS) across a 22-hour recording period. Pretreatment of rabbits with 25 [mu]g of IL-1RF blocked the somnogenic actions of 10 ng IL-1 given icv. Similarly, central pretreatment of animals with 25 [mu]g IL-1RF significantly attenuated the NREMS-promoting and REMS-suppressive actions of 150 pmol MDP injected centrally. The increase in NREMS and decrease in REMS induced by systemic injection of 12.5 [mu]g/kg MDP were also significantly suppressed by central administration of 50 [mu]g IL -1RF. In contrast, the febrile responses induced by either icv or iv injected MDP were not significantly affected by IL-1RF. These results support the hypothesis that endogenous, brain derived IL-1 contributes to the maintenance of normal sleep and may mediate sleep responses to systemic as well as central bacterial infections. 

Received 12 May 1995; accepted in final form 10 January 1996.
APS Manuscript Number R288-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96