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Am J Physiol Regul Integr Comp Physiol 280: R1806-R1814, 2001;
0363-6119/01 $5.00
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Vol. 280, Issue 6, R1806-R1814, June 2001

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

Linda A. Toth1 and Mark R. Opp2

1 Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois 62794; and 2 Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston, Texas 77555

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 waking. 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 phase 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 lipopolysaccharide (LPS). In IL-10 KO mice, LPS induced an initial transient increase and a subsequent prolonged decrease in SWS, as well as profound hypothermia. 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. Collectively, these observations support a role for IL-10 in sleep regulation and provide further evidence for the involvement of cytokines in the regulation of sleep.

interleukin-1; tumor necrosis factor; lipopolysaccharide; thermoregulation; influenza


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