Advertisement

Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation

  • Michael R. Irwin
    Correspondence
    Address correspondence to Michael R. Irwin, M.D., UCLA Semel Institute, Cousins Center for Psychoneuroimmunology, 300 UCLA Medical Plaza, Room 3130, Los Angeles, CA 90095-7076
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, University of California, Los Angeles, Los Angeles, California.

    Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.

    Department of Psychology, University of California, Los Angeles, Los Angeles, California.
    Search for articles by this author
  • Richard Olmstead
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, University of California, Los Angeles, Los Angeles, California.

    Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
    Search for articles by this author
  • Judith E. Carroll
    Affiliations
    Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, University of California, Los Angeles, Los Angeles, California.

    Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
    Search for articles by this author

      Abstract

      Background

      Sleep disturbance is associated with inflammatory disease risk and all-cause mortality. Here, we assess global evidence linking sleep disturbance, sleep duration, and inflammation in adult humans.

      Methods

      A systematic search of English language publications was performed, with inclusion of primary research articles that characterized sleep disturbance and/or sleep duration or performed experimental sleep deprivation and assessed inflammation by levels of circulating markers. Effect sizes (ES) and 95% confidence intervals (CI) were extracted and pooled using a random effect model.

      Results

      A total of 72 studies (n > 50,000) were analyzed with assessment of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNFα). Sleep disturbance was associated with higher levels of CRP (ES .12; 95% CI = .05–.19) and IL-6 (ES .20; 95% CI = .08–.31). Shorter sleep duration, but not the extreme of short sleep, was associated with higher levels of CRP (ES .09; 95% CI = .01–.17) but not IL-6 (ES .03; 95% CI: −.09 to .14). The extreme of long sleep duration was associated with higher levels of CRP (ES .17; 95% CI = .01–.34) and IL-6 (ES .11; 95% CI = .02–20). Neither sleep disturbances nor sleep duration was associated with TNFα. Neither experimental sleep deprivation nor sleep restriction was associated with CRP, IL-6, or TNFα. Some heterogeneity among studies was found, but there was no evidence of publication bias.

      Conclusions

      Sleep disturbance and long sleep duration, but not short sleep duration, are associated with increases in markers of systemic inflammation.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Dew M.A.
        • Hoch C.C.
        • Buysse D.J.
        • Monk T.H.
        • Begely A.E.
        • Houck P.R.
        • et al.
        Healthy older adults’ sleep predicts all-cause mortality at 4 to 19 years of follow-up.
        Psychosom Med. 2003; 65: 63-73
        • Kripke D.F.
        • Garfinkel L.
        • Wingard D.L.
        • Klauber M.R.
        • Marler M.R.
        Mortality associated with sleep duration and insomnia.
        Arch Gen Psychiatry. 2002; 59: 131-136
        • Mallon L.
        • Broman J.E.
        • Hetta J.
        Sleep complaints predict coronary artery disease mortality in males: A 12-year follow-up study of a middle-aged Swedish population.
        J Intern Med. 2002; 251: 207-216
        • Vgontzas A.N.
        • Fernandez-Mendoza J.
        • Liao D.
        • Bixler E.O.
        Insomnia with objective short sleep duration: The most biologically severe phenotype of the disorder.
        Sleep Med Rev. 2013; 17: 241-254
        • LeBlanc M.
        • Merette C.
        • Savard J.
        • Ivers H.
        • Baillargeon L.
        • Morin C.M.
        Incidence and risk factors of insomnia in a population-based sample.
        Sleep. 2009; 32: 1027-1037
        • Morin C.M.
        • Belanger L.
        • LeBlanc M.
        • Ivers H.
        • Savard J.
        • Espie C.A.
        • et al.
        The natural history of insomnia: A population-based 3-year longitudinal study.
        Arch Intern Med. 2009; 169: 447-453
        • Ohayon M.M.
        Epidemiology of insomnia: What we know and what we still need to learn.
        Sleep Med Rev. 2002; 6: 97-111
        • Buysse D.J.
        Sleep health: Can we define it? Does it matter?.
        Sleep. 2014; 37: 9-17
        • Irwin M.R.
        Why sleep is important for health: A psychoneuroimmunology perspective.
        Annu Rev Psychol 66. 2015; 2: 30
        • Ridker P.M.
        • Rifai N.
        • Rose L.
        • Buring J.E.
        • Cook N.R.
        Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.
        N Engl J Med. 2002; 347: 1557-1565
        • Ridker P.M.
        • Buring J.E.
        • Cook N.R.
        • Rifai N.
        C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: An 8-year follow-up of 14 719 initially healthy American women.
        Circulation. 2003; 107: 391-397
        • Sesso H.D.
        • Buring J.E.
        • Rifai N.
        • Blake G.J.
        • Gaziano J.M.
        • Ridker P.M.
        C-reactive protein and the risk of developing hypertension.
        JAMA. 2003; 290: 2945-2951
        • Barzilay J.I.
        • Forsberg C.
        • Heckbert S.R.
        • Cushman M.
        • Newman A.B.
        The association of markers of inflammation with weight change in older adults: The Cardiovascular Health Study.
        Int J Obes (Lond). 2006; 30: 1362-1367
        • Irwin M.R.
        • Cole S.W.
        Reciprocal regulation of the neural and innate immune systems.
        Nat Rev Immunol. 2011; 11: 625-632
        • Brunner E.J.
        • Kivimaki M.
        • Witte D.R.
        • Lawlor D.A.
        • Davey Smith G.
        • Cooper J.A.
        • et al.
        Inflammation, insulin resistance, and diabetes--Mendelian randomization using CRP haplotypes points upstream.
        PLoS Med. 2008; 5: e155
        • Irwin M.
        • Olmstead R.
        • Breen E.
        • Witarama T.
        • Carrillo C.
        • Sadeghi N.
        • et al.
        Tai Chi, cellular inflammation, and transcriptome dynamics in breast cancer survivors with insomnia: A randomized controlled trial.
        J Natl Cancer Inst Monogr. 2014; 50: 295-301
        • Irwin M.R.
        • Olmstead R.
        • Carrillo C.
        • Sadeghi N.
        • Breen E.C.
        • Witarama T.
        • et al.
        Cognitive behavioral therapy vs. Tai Chi for late life insomnia and inflammatory risk: A randomized controlled comparative efficacy trial.
        Sleep. 2014; 37: 1543-1552
        • Irwin M.R.
        • Olmstead R.
        • Breen E.C.
        • Witarama T.
        • Carrillo C.
        • Sadeghi N.
        • et al.
        Cognitive behavioral therapy and Tai Chi reverse cellular and genomic markers of inflammation in late life insomnia: A randomized controlled trial.
        Biol Psychiatry. 2015; 78: 721-729
        • Xie X.
        • Pan L.
        • Ren D.
        • Du C.
        • Guo Y.
        Effects of continuous positive airway pressure therapy on systemic inflammation in obstructive sleep apnea: A meta-analysis.
        Sleep Med. 2013; 14: 1139-1150
        • Erten Y.
        • Kokturk O.
        • Yuksel A.
        • Elbeg S.
        • Ciftci T.U.
        • Pasaoglu H.
        • et al.
        Relationship between sleep complaints and proinflammatory cytokines in haemodialysis patients.
        Nephrology (Carlton). 2005; 10: 330-335
        • Hong S.
        • Mills P.J.
        • Loredo J.S.
        • Adler K.A.
        • Dimsdale J.E.
        The association between interleukin-6, sleep, and demographic characteristics.
        Brain Behav Immun. 2005; 19: 165-172
        • Lee J.H.
        • Kim S.J.
        • Jung H.H.
        Nocturnal sleep related with metabolic markers in end-stage renal disease patients receiving hemodialysis.
        Psychiatry Investig. 2009; 6: 34-38
        • Mills P.J.
        • von Kanel R.
        • Norman D.
        • Natarajan L.
        • Ziegler M.G.
        • Dimsdale J.E.
        Inflammation and sleep in healthy individuals.
        Sleep. 2007; 30: 729-735
        • Sprod L.K.
        • Palesh O.G.
        • Janelsins M.C.
        • Peppone L.J.
        • Heckler C.E.
        • Adams M.J.
        • et al.
        Exercise, sleep quality, and mediators of sleep in breast and prostate cancer patients receiving radiation therapy.
        Community Oncol. 2010; 7: 463-471
        • von Kanel R.
        • Dimsdale J.E.
        • Ancoli-Israel S.
        • Mills P.J.
        • Patterson T.L.
        • McKibbin C.L.
        • et al.
        Poor sleep is associated with higher plasma proinflammatory cytokine interleukin-6 and procoagulant marker fibrin D-dimer in older caregivers of people with Alzheimer’s disease.
        J Am Geriatr Soc. 2006; 54: 431-437
        • Almeida O.P.
        • Alfonso H.
        • Yeap B.B.
        • Hankey G.
        • Flicker L.
        Complaints of difficulty to fall asleep increase the risk of depression in later life: The health in men study.
        J Affect Disord. 2011; 134: 208-216
        • Jackowska M.
        • Kumari M.
        • Steptoe A.
        Sleep and biomarkers in the English Longitudinal Study of Ageing: Associations with C-reactive protein, fibrinogen, dehydroepiandrosterone sulfate and hemoglobin.
        Psychoneuroendocrinology. 2013; 38: 1484-1493
        • Laugsand L.E.
        • Vatten L.J.
        • Bjorngaard J.H.
        • Hveem K.
        • Janszky I.
        Insomnia and high-sensitivity C-reactive protein: The HUNT study, Norway.
        Psychosom Med. 2012; 74: 543-553
        • Lavie L.
        • Lavie P.
        Elevated plasma homocysteine in older shift-workers: A potential risk factor for cardiovascular morbidity.
        Chronobiol Int. 2007; 24: 115-128
        • Liukkonen T.
        • Rasanen P.
        • Ruokonen A.
        • Laitinen J.
        • Jokelainen J.
        • Leinonen M.
        • et al.
        C-reactive protein levels and sleep disturbances: Observations based on the Northern Finland 1966 Birth Cohort study.
        Psychosom Med. 2007; 69: 756-761
        • McDade T.W.
        • Hawkley L.C.
        • Cacioppo J.T.
        Psychosocial and behavioral predictors of inflammation in middle-aged and older adults: The Chicago health, aging, and social relations study.
        Psychosom Med. 2006; 68: 376-381
        • Zhang J.
        • Lamers F.
        • Hickie I.B.
        • He J.P.
        • Feig E.
        • Merikangas K.R.
        Differentiating nonrestorative sleep from nocturnal insomnia symptoms: Demographic, clinical, inflammatory, and functional correlates.
        Sleep. 2013; 36: 671-679
        • Bower J.E.
        • Ganz P.A.
        • Tao M.L.
        • Hu W.
        • Belin T.R.
        • Sepah S.
        • et al.
        Inflammatory biomarkers and fatigue during radiation therapy for breast and prostate cancer.
        Clin Cancer Res. 2009; 15: 5534-5540
        • Burgos I.
        • Richter L.
        • Klein T.
        • Fiebich B.
        • Feige B.
        • Lieb K.
        • et al.
        Increased nocturnal interleukin-6 excretion in patients with primary insomnia: A pilot study.
        Brain Behav Immun. 2006; 20: 246-253
        • Chiu Y.L.
        • Chuang Y.F.
        • Fang K.C.
        • Liu S.K.
        • Chen H.Y.
        • Yang J.Y.
        • et al.
        Higher systemic inflammation is associated with poorer sleep quality in stable haemodialysis patients.
        Nephrol Dial Transplant. 2009; 24: 247-251
        • Christian L.M.
        • Glaser R.
        • Porter K.
        • Malarkey W.B.
        • Beversdorf D.
        • Kiecolt-Glaser J.K.
        Poorer self-rated health is associated with elevated inflammatory markers among older adults.
        Psychoneuroendocrinolgy. 2011; 36: 1495-1504
        • Clevenger L.
        • Schrepf A.
        • Christensen D.
        • DeGeest K.
        • Bender D.
        • Ahmed A.
        • et al.
        Sleep disturbance, cytokines, and fatigue in women with ovarian cancer.
        Brain Behav Immun. 2012; 26: 1037-1044
        • Dowd J.B.
        • Goldman N.
        • Weinstein M.
        Sleep duration, sleep quality, and biomarkers of inflammation in a Taiwanese population.
        Ann Epidemiol. 2011; 21: 799-806
        • Friedman E.M.
        • Hayney M.S.
        • Love G.D.
        • Urry H.L.
        • Rosenkranz M.A.
        • Davidson R.J.
        • et al.
        Social relationships, sleep quality, and interleukin-6 in aging women.
        Proc Natl Acad Sci U S A. 2005; 102: 18757-18762
        • Heffner K.L.
        • France C.R.
        • Trost Z.
        • Ng H.M.
        • Pigeon W.R.
        Chronic low back pain, sleep disturbance, and interleukin-6.
        Clin J Pain. 2011; 27: 35-41
        • Heffner K.L.
        • Ng H.M.
        • Suhr J.A.
        • France C.R.
        • Marshall G.D.
        • Pigeon W.R.
        • Moynihan J.A.
        Sleep disturbance and older adults’ inflammatory responses to acute stress.
        Am J Geriatr Psychiatry. 2012; 20: 744-752
        • Okun M.L.
        • Coussons-Read M.
        • Hall M.
        Disturbed sleep is associated with increased C-reactive protein in young women.
        Brain Behav Immun. 2009; 23: 351-354
        • Okun M.L.
        • Hall M.
        • Coussons-Read M.E.
        Sleep disturbances increase interleukin-6 production during pregnancy: Implications for pregnancy complications.
        Reprod Sci. 2007; 14: 560-567
        • Prather A.A.
        • Marsland A.L.
        • Hall M.
        • Neumann S.A.
        • Muldoon M.F.
        • Manuck S.B.
        Normative variation in self-reported sleep quality and sleep debt is associated with stimulated pro-inflammatory cytokine production.
        Biol Psychol. 2009; 82: 12-17
        • Suarez E.C.
        Self-reported symptoms of sleep disturbance and inflammation, coagulation, insulin resistance and psychosocial distress: Evidence for gender disparity.
        Brain Behav Immun. 2008; 22: 960-968
        • Valentine R.J.
        • Woods J.A.
        • McAuley E.
        • Dantzer R.
        • Evans E.M.
        The associations of adiposity, physical activity and inflammation with fatigue in older adults.
        Brain Behav Immun. 2011; 25: 1482-1490
        • van Mark A.
        • Weiler S.W.
        • Schroder M.
        • Otto A.
        • Jauch-Chara K.
        • Groneberg D.A.
        • et al.
        The impact of shift work induced chronic circadian disruption on IL-6 and TNF-alpha immune responses.
        J Occup Med Toxicol. 2010; 5: 18
        • von Kanel R.
        • Ancoli-Israel S.
        • Dimsdale J.E.
        • Mills P.J.
        • Mausbach B.T.
        • Ziegler M.G.
        • et al.
        Sleep and biomarkers of atherosclerosis in elderly Alzheimer caregivers and controls.
        Gerontology. 2010; 56: 41-50
        • Afshar R.
        • Emany A.
        • Saremi A.
        • Shavandi N.
        • Sanavi S.
        Effects of intradialytic aerobic training on sleep quality in hemodialysis patients.
        Iran J Kidney Dis. 2011; 5: 119-123
        • Bornivelli C.
        • Alivanis P.
        • Giannikouris I.
        • Arvanitis A.
        • Choustoulakis I.
        • Georgopoulou K.
        • et al.
        Relation between insomnia mood disorders and clinical and biochemical parameters in patients undergoing chronic hemodialysis.
        J Nephrol. 2008; 21: S78-S83
        • Bower J.E.
        • Ganz P.A.
        • Irwin M.R.
        • Kwan L.
        • Breen E.C.
        • Cole S.W.
        Inflammation and behavioral symptoms after breast cancer treatment: Do fatigue, depression, and sleep disturbance share a common underlying mechanism?.
        J Clin Oncol. 2011; 29: 3517-3522
        • Graff L.A.
        • Vincent N.
        • Walker J.R.
        • Clara I.
        • Carr R.
        • Ediger J.
        • et al.
        A population-based study of fatigue and sleep difficulties in inflammatory bowel disease.
        Inflamm Bowel Dis. 2011; 17: 1882-1889
        • Li J.
        • Guo Q.
        • Ye X.
        • Lin J.
        • Yi C.
        • Mao H.
        • et al.
        Prevalence and risk factors of sleep disturbance in continuous ambulatory peritoneal dialysis patients in Guangzhou, southern China.
        Int Urol Nephrol. 2012; 44: 929-936
        • Matthews K.A.
        • Zheng H.
        • Kravitz H.M.
        • Sowers M.
        • Bromberger J.T.
        • Buysse D.J.
        • et al.
        Are inflammatory and coagulation biomarkers related to sleep characteristics in mid-life women?: Study of Women’s Health across the Nation sleep study.
        Sleep. 2010; 33: 1649-1655
        • Razeghi E.
        • Sahraian M.A.
        • Heidari R.
        • Bagherzadeh M.
        Association of inflammatory biomarkers with sleep disorders in hemodialysis patients.
        Acta Neurol Belg. 2012; 112: 45-49
        • Sabbagh R.
        • Iqbal S.
        • Vasilevsky M.
        • Barre P.
        Correlation between physical functioning and sleep disturbances in hemodialysis patients.
        Hemodial Int. 2008; 12: S20-S24
        • Valentine R.J.
        • McAuley E.
        • Vieira V.J.
        • Baynard T.
        • Hu L.
        • Evans E.M.
        • Woods J.A.
        Sex differences in the relationship between obesity, C-reactive protein, physical activity, depression, sleep quality and fatigue in older adults.
        Brain Behav Immun. 2009; 23: 643-648
        • Okun M.L.
        • Reynolds 3rd, C.F.
        • Buysse D.J.
        • Monk T.H.
        • Mazumdar S.
        • Begley A.
        • Hall M.
        Sleep variability, health-related practices, and inflammatory markers in a community dwelling sample of older adults.
        Psychosom Med. 2011; 73: 142-150
        • Song C.
        • Lin A.
        • Bonaccorso S.
        • Heide C.
        • Verkerk R.
        • Kenis G.
        • et al.
        The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression.
        J Affect Disord. 1998; 49: 211-219
        • Vgontzas A.N.
        • Zoumakis M.
        • Papanicolaou D.A.
        • Bixler E.O.
        • Prolo P.
        • Lin H.M.
        • et al.
        Chronic insomnia is associated with a shift of interleukin-6 and tumor necrosis factor secretion from nighttime to daytime.
        Metabolism. 2002; 51: 887-892
        • Marsland A.L.
        • Gianaros P.J.
        • Abramowitch S.M.
        • Manuck S.B.
        • Hariri A.R.
        Interleukin-6 covaries inversely with hippocampal grey matter volume in middle-aged adults.
        Biol Psychiatry. 2008; 64: 484-490
        • Martinez-Gomez D.
        • Eisenmann J.C.
        • Gomez-Martinez S.
        • Hill E.E.
        • Zapatera B.
        • Veiga O.L.
        • et al.
        Sleep duration and emerging cardiometabolic risk markers in adolescents. The AFINOS study.
        Sleep Med. 2011; 12: 997-1002
        • Okun M.L.
        • Coussons-Read M.E.
        Sleep disruption during pregnancy: How does it influence serum cytokines?.
        J Reprod Immunol. 2007; 73: 158-165
        • Ramey S.L.
        • Perkhounkova Y.
        • Moon M.
        • Budde L.
        • Tseng H.C.
        • Clark M.K.
        The effect of work shift and sleep duration on various aspects of police officers’ health.
        Workplace Health Saf. 2012; 60: 215-222
        • Taheri S.
        • Austin D.
        • Lin L.
        • Nieto F.J.
        • Young T.
        • Mignot E.
        Correlates of serum C-reactive protein (CRP)--no association with sleep duration or sleep disordered breathing.
        Sleep. 2007; 30: 991-996
        • Taveras E.M.
        • Rifas-Shiman S.L.
        • Rich-Edwards J.W.
        • Mantzoros C.S.
        Maternal short sleep duration is associated with increased levels of inflammatory markers at 3 years postpartum.
        Metabolism. 2011; 60: 982-986
        • Motivala S.J.
        • Sarfatti A.
        • Olmos L.
        • Irwin M.R.
        Inflammatory markers and sleep disturbance in major depression.
        Psychosom Med. 2005; 67: 187-194
        • Rief W.
        • Mills P.J.
        • Ancoli-Israel S.
        • Ziegler M.G.
        • Pung M.A.
        • Dimsdale J.E.
        Overnight changes of immune parameters and catecholamines are associated with mood and stress.
        Psychosom Med. 2010; 72: 755-762
        • Vgontzas A.N.
        • Papanicolaou D.A.
        • Bixler E.O.
        • Kales A.
        • Tyson K.
        • Chrousos G.P.
        Elevation of plasma cytokines in disorders of excessive daytime sleepiness: Role of sleep disturbance and obesity.
        J Clin Endocrinol Metab. 1997; 82: 1313-1316
        • Larkin E.K.
        • Rosen C.L.
        • Kirchner H.L.
        • Storfer-Isser A.
        • Emancipator J.L.
        • Johnson N.L.
        • et al.
        Variation of C-reactive protein levels in adolescents: Association with sleep-disordered breathing and sleep duration.
        Circulation. 2005; 111: 1978-1984
        • Ferrie J.E.
        • Kivimaki M.
        • Akbaraly T.N.
        • Singh-Manoux A.
        • Miller M.A.
        • Gimeno D.
        • et al.
        Associations between change in sleep duration and inflammation: Findings on C-reactive protein and interleukin 6 in the Whitehall II Study.
        Am J Epidemiol. 2013; 178: 956-961
        • Miller M.A.
        • Kandala N.B.
        • Kivimaki M.
        • Kumari M.
        • Brunner E.J.
        • Lowe G.D.
        • et al.
        Gender differences in the cross-sectional relationships between sleep duration and markers of inflammation: Whitehall II study.
        Sleep. 2009; 32: 857-864
        • Patel S.R.
        • Zhu X.
        • Storfer-Isser A.
        • Mehra R.
        • Jenny N.S.
        • Tracy R.
        • Redline S.
        Sleep duration and biomarkers of inflammation.
        Sleep. 2009; 32: 200-204
        • Stenholm S.
        • Kronholm E.
        • Bandinelli S.
        • Guralnik J.M.
        • Ferrucci L.
        Self-reported sleep duration and time in bed as predictors of physical function decline: Results from the InCHIANTI study.
        Sleep. 2011; 34: 1583-1593
        • Tuomilehto H.
        • Peltonen M.
        • Partinen M.
        • Lavigne G.
        • Eriksson J.G.
        • Herder C.
        • et al.
        Sleep duration, lifestyle intervention, and incidence of type 2 diabetes in impaired glucose tolerance: The Finnish Diabetes Prevention Study.
        Diabetes Care. 2009; 32: 1965-1971
        • Cappuccio F.P.
        • D’Elia L.
        • Strazzullo P.
        • Miller M.A.
        Sleep duration and all-cause mortality: A systematic review and meta-analysis of prospective studies.
        Sleep. 2010; 33: 585-592
        • Cappuccio F.P.
        • Cooper D.
        • D’Elia L.
        • Strazzullo P.
        • Miller M.A.
        Sleep duration predicts cardiovascular outcomes: A systematic review and meta-analysis of prospective studies.
        Eur Heart J. 2011; 32: 1484-1492
        • Chennaoui M.
        • Sauvet F.
        • Drogou C.
        • Van Beers P.
        • Langrume C.
        • Guillard M.
        • et al.
        Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men.
        Cytokine. 2011; 56: 318-324
        • Faraut B.
        • Boudjeltia K.Z.
        • Dyzma M.
        • Rousseau A.
        • David E.
        • Stenuit P.
        • et al.
        Benefits of napping and an extended duration of recovery sleep on alertness and immune cells after acute sleep restriction.
        Brain Behav Immun. 2011; 25: 16-24
        • Frey D.J.
        • Fleshner M.
        • Wright Jr, K.P.
        The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults.
        Brain Behav Immun. 2007; 21: 1050-1057
        • Sauvet F.
        • Leftheriotis G.
        • Gomez-Merino D.
        • Langrume C.
        • Drogou C.
        • Van Beers P.
        • et al.
        Effect of acute sleep deprivation on vascular function in healthy subjects.
        J Appl Physiol. 2010; 108: 68-75
        • Abedelmalek S.
        • Chtourou H.
        • Aloui A.
        • Aouichaoui C.
        • Souissi N.
        • Tabka Z.
        Effect of time of day and partial sleep deprivation on plasma concentrations of IL-6 during a short-term maximal performance.
        Eur J Appl Physiol. 2013; 113: 241-248
        • Bollinger T.
        • Bollinger A.
        • Oster H.
        • Solbach W.
        Sleep, immunity, and circadian clocks: A mechanistic model.
        Gerontology. 2010; 56: 574-580
        • Haack M.
        • Kraus T.
        • Schuld A.
        • Dalal M.
        • Koethe D.
        • Pollmacher T.
        Diurnal variations of interleukin-6 plasma levels are confounded by blood drawing procedures.
        Psychoneuroendocrinology. 2002; 27: 921-931
        • Irwin M.
        • Rinetti G.
        • Redwine L.
        • Motivala S.
        • Dang J.
        • Ehlers C.
        Nocturnal proinflammatory cytokine-associated sleep disturbances in abstinent African American alcoholics.
        Brain Behav Immun. 2004; 18: 349-360
        • Redwine L.
        • Hauger R.L.
        • Gillin J.C.
        • Irwin M.
        Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans.
        J Clin Endocrinol Metab. 2000; 85: 3597-3603
        • Vgontzas A.N.
        • Papanicolaou D.A.
        • Bixler E.O.
        • Lotsikas A.
        • Zachman K.
        • Kales A.
        • et al.
        Circadian interleukin-6 secretion and quantity and depth of sleep.
        J Clin Endocrinol Metab. 1999; 84: 2603-2607
        • Vgontzas A.N.
        • Pejovic S.
        • Zoumakis E.
        • Lin H.M.
        • Bixler E.O.
        • Basta M.
        • et al.
        Daytime napping after a night of sleep loss decreases sleepiness, improves performance, and causes beneficial changes in cortisol and interleukin-6 secretion.
        Am J Physiol Endocrinol Metab. 2007; 292: E253-E261
        • Haack M.
        • Sanchez E.
        • Mullington J.M.
        Elevated inflammatory markers in response to prolonged sleep restriction are associated with increased pain experience in healthy volunteers.
        Sleep. 2007; 30: 1145-1152
        • Meier-Ewert H.K.
        • Ridker P.M.
        • Rifai N.
        • Regan M.M.
        • Price N.J.
        • Dinges D.F.
        • Mullington J.M.
        Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk.
        J Am Coll Cardiol. 2004; 43: 678-683
        • van Leeuwen W.M.
        • Lehto M.
        • Karisola P.
        • Lindholm H.
        • Luukkonen R.
        • Sallinen M.
        • et al.
        Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP.
        PLoS One. 2009; 4: e4589
        • Schmid S.M.
        • Hallschmid M.
        • Jauch-Chara K.
        • Wilms B.
        • Lehnert H.
        • Born J.
        • Schultes B.
        Disturbed glucoregulatory response to food intake after moderate sleep restriction.
        Sleep. 2011; 34: 371-377
        • Shearer W.T.
        • Reuben J.M.
        • Mullington J.M.
        • Price N.J.
        • Lee B.N.
        • Smith E.O.
        • et al.
        Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight.
        J Allergy Clin Immunol. 2001; 107: 165-170
        • Vgontzas A.N.
        • Zoumakis E.
        • Bixler E.O.
        • Lin H.M.
        • Follett H.
        • Kales A.
        • Chrousos G.P.
        Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines.
        J Clin Endocrinol Metab. 2004; 89: 2119-2126
        • Downs S.H.
        • Black N.
        The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions.
        J Epidemiol Community Health. 1998; 52: 377-384
        • Wilson D.B.
        • Lipsey M.W.
        The role of method in treatment effectiveness research: Evidence from meta-analysis.
        Psychol Methods. 2001; 6: 413-429
        • Higgins J.P.
        • Thompson S.G.
        • Deeks J.J.
        • Altman D.G.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Egger M.
        • Davey Smith G.
        • Schneider M.
        • Minder C.
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • Foster S.B.
        • Lu M.
        • Glaze D.G.
        • Reuben J.M.
        • Harris L.L.
        • Cohen E.N.
        • et al.
        Associations of cytokines, sleep patterns, and neurocognitive function in youth with HIV infection.
        Clin Immunol. 2012; 144: 13-23
        • Main L.C.
        • Dawson B.
        • Heel K.
        • Grove J.R.
        • Landers G.J.
        • Goodman C.
        Relationship between inflammatory cytokines and self-report measures of training overload.
        Res Sports Med. 2010; 18: 127-139
        • Capuron L.
        • Schroecksnadel S.
        • Féart C.
        • Aubert A.
        • Higueret D.
        • Barberger-Gateau P.
        • et al.
        Chronic low-grade inflammation in elderly persons is associated with altered tryptophan and tyrosine metabolism: Role in neuropsychiatric symptoms.
        Biol Psychiatry. 2011; 70: 175-182
        • Cho H.J.
        • Bower J.E.
        • Kiefe C.I.
        • Seeman T.E.
        • Irwin M.R.
        Early life stress and inflammatory mechanisms of fatigue in the Coronary Artery Risk Development in Young Adults (CARDIA) study.
        Brain Behav Immun. 2012; 26: 859-865
        • Liu L.
        • Mills P.J.
        • Rissling M.
        • Fiorentino L.
        • Natarajan L.
        • Dimsdale J.E.
        • et al.
        Fatigue and sleep quality are associated with changes in inflammatory markers in breast cancer patients undergoing chemotherapy.
        Brain Behav Immun. 2012; 26: 706-713
        • von Käanel R.
        • Mausbach B.T.
        • Ancoli-Israel S.
        • Dimsdale J.E.
        • Mills P.J.
        • Patterson T.L.
        • et al.
        Sleep in spousal Alzheimer caregivers: A longitudinal study with a focus on the effects of major patient transitions on sleep.
        Sleep. 2012; 35: 247-255
        • Vgontzas A.N.
        • Zoumakis M.
        • Bixler E.O.
        • Lin H.M.
        • Prolo P.
        • Vela-Bueno A.
        • et al.
        Impaired nighttime sleep in healthy old versus young adults is associated with elevated plasma interleukin-6 and cortisol levels: Physiologic and therapeutic implications.
        J Clin Endocrinol Metab. 2003; 88: 2087-2095
        • Carpagnano G.E.
        • Spanevello A.
        • Sabato R.
        • Depalo A.
        • Palladino G.P.
        • Bergantino L.
        • Foschino Barbaro M.P.
        Systemic and airway inflammation in sleep apnea and obesity: The role of ICAM-1 and IL-8.
        Transl Res. 2010; 155: 35-43
        • Hohagen F.
        • Timmer J.
        • Weyerbrock A.
        • Ritsch-Montero R.
        • Ganter U.
        • Krieger S.
        • et al.
        Cytokine production during sleep and wakefulness and its relationship to cortisol in healthy humans.
        Neuropsychobiology. 1993; 28: 9-16
        • Sakami S.
        • Ishikawa T.
        • Kawakami N.
        • Haratani T.
        • Fukui A.
        • Kobayashi F.
        • et al.
        Coemergence of insomnia and a shift in the Th1/Th2 balance toward Th2 dominance.
        Neuroimmunomodulation. 2002; 10: 337-343
        • Cole S.W.
        • Arevalo J.M.
        • Manu K.
        • Telzer E.H.
        • Kiang L.
        • Bower J.E.
        • et al.
        Antagonistic pleiotropy at the human IL6 promoter confers genetic resilience to the pro-inflammatory effects of adverse social conditions in adolescence.
        Dev Psychol. 2011; 47: 1173-1180
        • Prather A.A.
        • Epel E.S.
        • Cohen B.E.
        • Neylan T.C.
        • Whooley M.A.
        Gender differences in the prospective associations of self-reported sleep quality with biomarkers of systemic inflammation and coagulation: Findings from the Heart and Soul Study.
        J Psychiatr Res. 2013; 47: 1228-1235
        • Irwin M.R.
        • Wang M.
        • Ribeiro D.
        • Cho H.J.
        • Olmstead R.
        • Breen E.C.
        • et al.
        Sleep loss activates cellular inflammatory signaling.
        Biol Psychiatry. 2008; 64: 538-540
        • Irwin M.R.
        • Carrillo C.
        • Olmstead R.
        Sleep loss activates cellular markers of inflammation: Sex differences.
        Brain Behav Immun. 2010; 24: 54-57
        • O’Connor M.F.
        • Motivala S.J.
        • Valladares E.M.
        • Olmstead R.
        • Irwin M.R.
        Sex differences in monocyte expression of IL-6: Role of autonomic mechanisms.
        Am J Physiol Regul Integr Comp Physiol. 2007; 293: R145-R151
        • Whitacre C.C.
        Sex differences in autoimmune disease.
        Nat Immunol. 2001; 2: 777-780
        • Cappuccio F.P.
        • Stranges S.
        • Kandala N.B.
        • Miller M.A.
        • Taggart F.M.
        • Kumari M.
        • et al.
        Gender-specific associations of short sleep duration with prevalent and incident hypertension: The Whitehall II Study.
        Hypertension. 2007; 50: 693-700
        • Newman A.B.
        • Spiekerman C.F.
        • Enright P.
        • Lefkowitz D.
        • Manolio T.
        • Reynolds C.F.
        • Robbins J.
        Daytime sleepiness predicts mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group.
        J Am Geriatr Soc. 2000; 48: 115-123
        • Carroll J.E.
        • Seeman T.E.
        • Olmstead R.
        • Melendez G.
        • Sadakane R.
        • Bootzin R.
        • et al.
        Improved sleep quality in older adults with insomnia reduces biomarkers of disease risk: Pilot results from a randomized controlled comparative efficacy trial.
        Psychoneuroendocrinology. 2015; 55: 184-192
        • Carroll J.E.
        • Irwin M.R.
        • Stein Merkin S.
        • Seeman T.E.
        Sleep and multisystem biological risk: A population-based study.
        PLoS One. 2015; 10: e0118467
        • Vgontzas A.N.
        • Liao D.
        • Pejovic S.
        • Calhoun S.
        • Karataraki M.
        • Basta M.
        • et al.
        Insomnia with short sleep duration and mortality: The Penn State cohort.
        Sleep. 2010; 33: 1159-1164
        • Vgontzas A.N.
        • Liao D.
        • Bixler E.O.
        • Chrousos G.P.
        • Vela-Bueno A.
        Insomnia with objective short sleep duration is associated with a high risk for hypertension.
        Sleep. 2009; 32: 491-497
        • Kierlin L.
        • Olmstead R.
        • Yokomizo M.
        • Nicassio P.
        • Irwin M.R.
        Diagnostic and Statistical Manual criteria for insomnia related impairment in daytime functioning: Polysomnographic correlates in older adults.
        Sleep Med. 2012; 13: 958-960
        • Irwin M.R.
        • Wang M.
        • Campomayor C.O.
        • Collado-Hidalgo A.
        • Cole S.
        Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation.
        Arch Intern Med. 2006; 166: 1756-1762
        • Slavich G.M.
        • Irwin M.R.
        From stress to inflammation and major depressive disorder: A social signal transduction theory of depression.
        Psychol Bull. 2014; 140: 774-815
        • Irwin M.
        • Thompson J.
        • Miller C.
        • Gillin J.C.
        • Ziegler M.
        Effects of sleep and sleep deprivation on catecholamine and interleukin-2 levels in humans: Clinical implications.
        J Clin Endocrin Metab. 1999; 84: 1979-1985
        • Signal T.L.
        • Gale J.
        • Gander P.H
        Sleep measurement in flight crew: Comparing actigraphic and subjective estimates to polysomnography.
        Aviat Space Environ Med. 2005; 76: 1058-1063
        • Patel S.R.
        • Ayas N.T.
        • Malhotra M.R.
        • White D.P.
        • Schernhammer E.S.
        • Speizer F.E.
        • et al.
        A prospective study of sleep duration and mortality risk in women.
        Sleep. 2004; 27: 440-444