An interleukin-1 receptor fragment inhibits spontaneous sleep and muramyl dipeptide-induced sleep in rabbits.
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 N-acetylmuramyl-L-alanyl-D-isoglutamine (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 and 50 micrograms) were injected into normal rabbits intracerebroventricularly (icv). Both doses significantly decreased spontaneous non-rapid eye movement sleep (NREMS) across a 22-h recording period. Pretreatment of rabbits with 25 micrograms of IL-1RF blocked the somnogenic actions of 10 ng icv IL-1. Similarly, central pretreatment of animals with 25 micrograms 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 micrograms/kg MDP were also significantly suppressed by central administration of 50 micrograms IL-1RF. In contrast, the febrile response induced by either intracerebroventricularly or intravenously 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.
Takahashi
S
S
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.
Kapás
L
L
Fang
J
J
Seyer
J M
JM
Wang
Y
Y
Krueger
J M
JM
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D007267:Injections; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000737:chemistry*; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects
D007375:Interleukin-1; D010446:Peptide Fragments; D017472:Receptors, Interleukin-1; D000119:Acetylmuramyl-Alanyl-Isoglutamine