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.

  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adult mammalian brains continuously generate new neurons, a phenomenon called neurogenesis. Both environmental stimuli and endogenous factors are important regulators of neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and neurogenesis in brain function, such as learning, memory and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on neurogenesis.
    Frontiers in Cellular Neuroscience 03/2015; 9:140. DOI:10.3389/fncel.2015.00140 · 4.18 Impact Factor
  • Source
    • "One of the most intensely investigated biological mechanisms underlying these effects is systemic inflammation (Irwin, 2015; Motivala, 2011). Plasma levels of inflammatory markers have been shown to be elevated in clinical populations with sleep disturbance – e.g., end stage renal disease, alcoholism, and major depression (Chiu et al., 2009; Irwin et al., 2004; Motivala et al., 2005) – and also following experimental sleep deprivation (Irwin et al., 2006, 2008). However, less is known about the relationships between sleep disturbance and systemic inflammation in community-dwelling adults. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Both sleep disturbance and social isolation increase the risk for morbidity and mortality. Systemic inflammation is suspected as a potential mechanism of these associations. However, the complex relationships between sleep disturbance, social isolation, and inflammation have not been examined in a population-based longitudinal study. This study examined the longitudinal association between sleep disturbance and systemic inflammation, and the moderating effects of social isolation on this association. The CARDIA study is a population-based longitudinal study conducted in four US cities. Sleep disturbance - i.e., insomnia complaints and short sleep duration - was assessed in 2962 African-American and white adults at baseline (2000-2001, ages 33-45 years). Circulating C-reactive protein (CRP) was measured at baseline and follow-up (2005-2006). Interleukin-6 (IL-6) and subjective and objective social isolation (i.e., feelings of social isolation and social network size) were measured at follow-up. Sleep disturbance was a significant predictor of inflammation five years later after full adjustment for covariates (adjusted betas: 0.048, P=0.012 for CRP; 0.047, P=0.017 for IL-6). Further adjustment for baseline CRP revealed that sleep disturbance also impacted the longitudinal change in CRP levels over five years (adjusted beta: 0.044, P=0.013). Subjective social isolation was a significant moderator of this association between sleep disturbance and CRP (adjusted beta 0.131, P=0.002). Sleep disturbance was associated with heightened systemic inflammation in a general population over a five-year follow-up, and this association was significantly stronger in those who reported feelings of social isolation. Clinical interventions targeting sleep disturbances may be a potential avenue for reducing inflammation, particularly in individuals who feel socially isolated. Copyright © 2015. Published by Elsevier Inc.
    Brain Behavior and Immunity 02/2015; 46. DOI:10.1016/j.bbi.2015.02.023 · 6.13 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sleep occurs in a wide range of animal species as a vital process for the maintenance of homeostasis, metabolic restoration, physiological regulation, and adaptive cognitive functions in the central nervous system. Long-term perturbations induced by the lack of sleepSleep are mostly mediated by changes at the level of transcription and translation. This chapter reviews studies in humans, rodents, and flies to address the various ways by which sleep deprivation affects gene expressionGene expression in the nervous system, with a focus on genes related to neuronal plasticity, brain function, and cognitionCognition . However, the effects of sleep deprivation on gene expression and the functional consequences of sleep loss are clearly not restricted to the cognitive domain but may include increased inflammationInflammation , expression of stress-related genes, general impairment of protein translation, metabolic imbalance, and thermalThermoregulation deregulation.
Show more


Available from