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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 280; no. 6; pp. 1806 - R1814
• Main Authors: Toth, Linda A, Opp, Mark R
• Format: Journal Article
• Language: English
• Published: United States 01.06.2001
• Subjects: Animals; Body Temperature; Cytokines - pharmacology; Interleukin-1 - pharmacology; Interleukin-10 - deficiency; Interleukin-10 - genetics; Lipopolysaccharides - pharmacology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout - genetics; Motor Activity - physiology; Orthomyxoviridae Infections - physiopathology; Sleep - drug effects; Sleep - physiology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.2001.280.6.r1806

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