AN INTERLEUKIN-1 RECEPTOR FRAGMENT INHIBITS SPONTANEOUS SLEEP AND MURAMYL DIPEPTIDE-INDUCED SLEEP IN RABBITS

Interleukin-1 (IL-1) is hyothesized to be involved in physiological sl eep regulation and in sleep responses occurring during infectious dise ase. If this hypothesis is correct, then inhibition of endogenous IL-1 should reduce both normal sleep and N-acetylmuramyl-L-alanyl-D-isoglu tamine (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 hu man 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 (2 5 and 50 mu g) were injected into normal rabbits intracerebroventricul arly (icy). Both doses significantly decreased spontaneous non-rapid e ye movement sleep (NREMS) across a 22-h recording period. Pretreatment of rabbits with 25 mu g of IL-1RF blocked the somnogenic actions of 1 0 ng icv IL-1. Similarly, central pretreatment of animals with 25 mu g IL-1RF significantly attenuated the NREMS-promoting and REMS-suppress ive 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 intrac erebroventricularly or intravenously injected MDP were not significant ly affected by IL-1RF. These results support the hypothesis that endog enous, brain-derived IL-1 contributes to the maintenance of normal sle ep and may mediate sleep responses to systemic as well as central bact erial infections.