Article

Sleep deprivation and activation of morning levels of cellular and genomic markers

Department of Psychiatry and Biobehavioural Sciences, University of California, Los Angeles, Los Ángeles, California, United States
Archives of Internal Medicine (Impact Factor: 13.25). 10/2006; 166(16):1756-62. DOI: 10.1001/archinte.166.16.1756
Source: PubMed

ABSTRACT Inflammation is associated with increased risk of cardiovascular disorders, arthritis, diabetes mellitus, and mortality. The effects of sleep loss on the cellular and genomic mechanisms that contribute to inflammatory cytokine activity are not known.
In 30 healthy adults, monocyte intracellular proinflammatory cytokine production was repeatedly assessed during the day across 3 baseline periods and after partial sleep deprivation (awake from 11 pm to 3 am). We analyzed the impact of sleep loss on transcription of proinflammatory cytokine genes and used DNA microarray analyses to characterize candidate transcription-control pathways that might mediate the effects of sleep loss on leukocyte gene expression.
In the morning after a night of sleep loss, monocyte production of interleukin 6 and tumor necrosis factor alpha was significantly greater compared with morning levels following uninterrupted sleep. In addition, sleep loss induced a more than 3-fold increase in transcription of interleukin 6 messenger RNA and a 2-fold increase in tumor necrosis factor alpha messenger RNA. Bioinformatics analyses suggested that the inflammatory response was mediated by the nuclear factor kappaB inflammatory signaling system as well as through classic hormone and growth factor response pathways.
Sleep loss induces a functional alteration of the monocyte proinflammatory cytokine response. A modest amount of sleep loss also alters molecular processes that drive cellular immune activation and induce inflammatory cytokines; mapping the dynamics of sleep loss on molecular signaling pathways has implications for understanding the role of sleep in altering immune cell physiologic characteristics. Interventions that target sleep might constitute new strategies to constrain inflammation with effects on inflammatory disease risk.

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    • "Adecreaseofcellproliferationaftersleepdeprivationcan beassociatedtoenhancedlevelsofpro-inflammatorycytokines, interleukin(IL)-6andtumornecrosisfactor(TNF-a).Thereare evidencesthatbothIL-6andTNF-aareincreasedafterchronic sleepdeprivation(Irwinetal.,2006;Haacketal.,2007),andIL- 6plasmalevelsareenhancedinpatientswithinsomnia(Burgos etal.,2006).Invitro,exposuretoIL-6andTNF-adiminishes cellproliferationand,invivo,theycanmodulatethedamag- ingeffectsofneuroinflammationinhippocampalneurogenesis (Monjeetal.,2003). Themechanismbywhichprolongedsleepdeprivationaffects adultneurogenesismayimplyacomplexgroupofinteracting factors(Figure1),whichmay,infact,affectselectivelydifferent stagesofneurogenesisprocess(Meerloetal.,2009). "
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    • "In humans, one night of sleep loss leads to increased levels of IL-6 and TNFalpha (Irwin et al. 2006). Chronic sleep loss for 1 week in young adults leads to increased levels of IL-6 in both males and females, while TNF-alpha is increased only in men (Vgontzas et al. 2004). "
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