Cytokine- and microbially induced sleep responses of interleukin-10 deficient mice

Interleukin (IL)-1 and tumor necrosis factor (TNF) promote slow-wave sleep (SWS), whereas IL-10 inhibits the synthesis of IL-1 and TNF and promotes wa king. We evaluated the impact of endogenous IL-10 on sleep-wake behavior by studying mice that lack a functional IL-10 gene. Under baseline conditions , C57BL/6-IL-10 knockout (KO) mice spent more time in SWS during the dark p hase of the light-dark cycle than did genetically intact C57BL/6 mice. The two strains of mice showed generally comparable responses to treatment with IL-1, IL-10, or influenza virus, but differed in their responses to lipopo lysaccharide (LPS). In IL-10 KO mice, LPS induced an initial transient incr ease and a subsequent prolonged decrease in SWS, as well as profound hypoth ermia. These responses were not observed in LPS-treated C57BL/6 mice. These data demonstrate that in the absence of endogenous IL-10, spontaneous SWS is increased and the impact of LPS on vigilance states is altered. Collecti vely, these observations support a role for IL-10 in sleep regulation and p rovide further evidence for the involvement of cytokines in the regulation of sleep.