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: 17.33). 10/2006; 166(16):1756-62. DOI: 10.1001/archinte.166.16.1756
Source: PubMed


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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    • "Total daily sleep time is reduced and sleep becomes increasingly disrupted with aging (Ancoli-Israel, 2009; Bliwise, 1993; Edwards et al., 2010). Sleep disruption of healthy young and older adults is associated with increased production of inflammatory mediators (Frey et al., 2007; Haack et al., 2007; Irwin et al., 2006; Mullington et al., 2009; Simpson and Dinges, 2007; Vgontzas et al., 2003), including the cytokine tumor necrosis factor-a (TNF). As such, sleep disruption in the elderly may contribute to, or exacerbate sepsis outcomes because of the inflammatory state it induces. "
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    ABSTRACT: The factors by which aging predisposes to critical illness are varied, complex, and not well understood. Sepsis is considered a quintessential disease of old age because the incidence and mortality of severe sepsis increases in old and the oldest old individuals. Aging is associated with dramatic changes in sleep quality and quantity and sleep increasingly becomes fragmented with age. In healthy adults, sleep disruption induces inflammation. Multiple aspects of aging and of sleep dysregulation interact via neuroimmune mechanisms. Tumor necrosis factor-α (TNF), a cytokine involved in sleep regulation and neuroimmune processes, exerts some of its effects on the CNS by crossing the blood-brain barrier (BBB). In this study we examined the impact of sepsis, sleep fragmentation, and aging on BBB disruption and TNF transport into brain. We used the cecal ligation and puncture (CLP) model of sepsis in young and aged mice that were either undisturbed or had their sleep disrupted. There was a dichotomous effect of sepsis and sleep disruption with age: sepsis disrupted the BBB and increased TNF transport in young mice but not in aged mice, whereas sleep fragmentation disrupted the BBB and increased TNF transport in aged mice, but not in young mice. Combining sleep fragmentation and CLP did not produce a greater effect on either of these BBB parameters than did either of these manipulations alone. These results suggest that the mechanisms by which sleep fragmentation and sepsis alter BBB functions are fundamentally different from one another and that a major change in the organism's responses to those insults occurs with aging. Copyright © 2015. Published by Elsevier Inc.
    Brain Behavior and Immunity 07/2015; DOI:10.1016/j.bbi.2015.07.023 · 5.89 Impact Factor
    • "molecules (Aho et al., 2013; Irwin et al., 2006, 2008). "
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    ABSTRACT: Exposure to traffic noise may result in stress and sleep disturbances, which have been associated with impairment of the immune system. People with weakened immune systems are known to have a higher risk for non-Hodgkin lymphoma (NHL). We aimed to determine whether traffic noise was associated with risk for NHL in a nationwide case-control study. We identified 2753 cases aged 30-84 years with a primary diagnosis of NHL in Denmark between 1992 and 2010. For each case we selected two random population controls, matched on sex and year of birth. Road traffic and railway noise were calculated, and airport noise was estimated for all present and historical residential addresses of cases and controls from 1987 to 2010. Associations between traffic noise and risk for NHL were estimated using conditional logistic regression, adjusted for disposable income, education, cohabiting status and comorbidity. We found that a 5-year time-weighted mean of road traffic noise above 65dB was associated with an 18% higher risk for NHL (95% confidence interval (CI) 1.01-1.37) when compared to road traffic noise below 55dB, whereas for exposure between 55 and 65dB no association was found (odds ratio: 0.98; 95% CI: 0.88-1.08). In analyzes of NHL subtypes, we found no association between road traffic noise and risk for T-cell lymphoma, whereas increased risks for B-cell lymphoma and unspecified lymphomas were observed at exposures above 65dB. In conclusion, our nationwide study may indicate that high exposure to traffic noise is associated with higher NHL risk. Copyright © 2015 Elsevier Inc. All rights reserved.
    Environmental Research 06/2015; 142:61-65. DOI:10.1016/j.envres.2015.06.016 · 4.37 Impact Factor
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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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    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 · 4.29 Impact Factor
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