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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    • "Sleep interferes with the immune system and the inflammatory response[4]and in a study of 30 adults who were sleep deprived (sleep limited to 3 a.m. to 7 a.m.), researchers found monocyte production of interleukin-6 and tumor necrosis factor alpha to be significantly increased[14]; however, in a study of 19 participants who underwent 40 hours of total sleep deprivation, although there was a significant increase in interleukin-1beta and interleukin-1ra, there was a significant decrease in c-reactive protein and interleukin-6[15]. There is a need to further study the influence of routine sleep patterns upon the biological markers. "
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    ABSTRACT: Purpose. Previous research has indicated the public health impact of inadequate sleep duration on health, potentially through an immune-inflammation mechanism. This mechanism also has a role in periodontitis. The purpose of this study is to determine if there is an association of routine inadequate sleep and periodontitis. Methods. Data from merged National Health and Nutrition Examination Survey years 2009-10 and 2011-12 were the data source for the study. The key outcome was periodontitis (yes, no), and the key variable of interest was usual sleep on weekday or workday nights. Chi square and logistic regression procedures were conducted. The study included 3,740 participants who were of ages 30 years and above. Results. There were 52.7% of participants who had periodontitis. There were 35.7% who usually slept less than 7 hours on weekday or workday nights. In adjusted logistic regression the odds ratio for periodontal disease for participants who slept less than 7 hours on weekday or workday night was 1.00 [95% confidence interval: 0.83, 1.21; p = . 9812 ]. Conclusions. The relationship of periodontitis and inadequate sleep duration in a nationally representative study of participants who were of ages 30 years and above failed to reach statistical significance in adjusted logistic regression analyses.
    Full-text · Article · Jan 2016
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    • "Sleep loss has been associated with increased inflammation in humans and acts as a risk factor for development of chronic disease, notably cardiovascular and metabolic chronic diseases[8,21,25]. Although the exact mechanisms linking sleep loss to these various pathologies are incompletely understood, epidemiological and empirical studies have suggested that sleep loss promotes exaggerated inflammatory responses in brain and in the periphery[13,14,30,31]. Abbreviations: IL-1, interleukin-1-beta; MMP, modified multiple platform; PSD, paradoxical sleep deprivation; REM, rapid-eye movement; TGF1, transforming growth factor-beta-1; TNF, tumor necrosis factor-alpha. "
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    ABSTRACT: Sleep loss increases inflammatory mediators in brain and peripheral tissues, but the mechanisms underlying this association are not fully understood. Male C57BL/6j mice were exposed to paradoxical sleep deprivation (PSD) for 24 h using the modified multiple platform (MMP) technique (platforms over water) or two different controls: home cage or a dry platform cage, which constituted a novel environment. PSD mice exhibited increased IL-1β and TNF-α pro-inflammatory gene expression in brain (hypothalamus, hippocampus, pre-frontal cortex), as well as in peripheral tissues (liver, spleen), when compared with home-cage controls. In addition, among PSD mice, TGFβ1, an anti-inflammatory cytokine, was increased in pre-frontal cortex, liver, and spleen in conjunction with elevated serum corticosterone concentration relative to home-cage controls. However, these differences were nearly abolished when PSD mice were compared with control mice subjected to a dry MMP cage, suggesting that simply exposing mice to a novel environment can induce an acute inflammatory response.
    Full-text · Article · Jan 2016 · Neuroscience Letters
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    • "In shorter human experiments the results were not so consistent (reviewed in Motivala 2011). However, even 1 day of partial sleep deprivation produces many short lasting disturbances in immunity, like reduction of activity of natural killers and lymphokine-activated killers or the suppression of IL-2 production (Irwin et al. 2006). The important implication from human studies is that adequate sleep period shortens the time of viral infection (Cohen et al. 2009). "
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    ABSTRACT: Many psychiatric disorders, like schizophrenia, affective disorders, addictions and different forms of dementia are associated with sleep disturbances. In the etiology and course of those diseases inflammatory processes are regarded to be an increasingly important factor. They are also a frequently discussed element of the pathology of sleep. In this literature review reports on correlations between poor sleep and inflammatory responses in various psychiatric conditions are discussed. The link between schizophrenia, affective disorders and inflammatory cytokines is a complex phenomenon, which has been already confirmed in a number of studies. However, the presence of sleep deficits in those conditions, being a common symptom of depression and psychoses, can be an additional factor having a considerable impact on the immunological processes in mental illnesses. In the analyzed data, a number of studies are presented describing the role of inflammatory markers in sleep disturbances and psychopathological symptoms of affective, psychotic, neurogenerative and other disorders. Also attention is drawn to possible implications for their treatment. Efforts to use, e.g., anti-inflammatory agents in psychiatry in the context of their impact on sleep are reported. The aspect of inflammatory markers in the role of sleep deprivation as the treatment method in major depressive disorder is also discussed. A general conclusion is drawn that the improvement of sleep quality plays a crucial role in the care for psychiatric patients.
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