This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vgontzas, A. N. Articles by Chrousos, G. P. Search for Related Content PubMed PubMed Citation Articles by Vgontzas, A. N. Articles by Chrousos, G. P.

Circadian Interleukin-6 Secretion and Quantity and Depth of Sleep

Sleep Research and Treatment Center (A.N.V., E.O.B., A.K.), Department of Psychiatry, Pennsylvania State University, Hershey, Pennsylvania 17033; Developmental Endocrinology Branch (D.A.P., A.L., K.Z., G.P.C.), National Institute of Child Health Development, National Institutes of Health, Bethesda, Maryland 20892; Clinical Neuroendocrinology Branch (P.P., M.-L.W., J.L., P.W.G.), National Institute for Mental Health, Bethesda, Maryland 20892; Bioengineering and Chronobiology Laboratories (R.C.H.), ETSI Telecommunications, Campus Universitario Vigo, Pontevedra 36200, Spain; and Endocrine Unit (G.M.), Evgenidion Hospital, Athens University, Athens 11528, Greece

Address all correspondence and requests for reprints to: Alexandros N. Vgontzas, M.D., Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033. E-mail: axv3{at}psu.edu

Patients with pathologically increased daytime sleepiness and fatigue have elevated levels of circulating interleukin-6 (IL-6). The latter is an inflammatory cytokine, which causes sickness manifestations, including somnolence and fatigue, and activation of the hypothalamic-pituitary-adrenal axis. In this study, we examined: 1) the relation between serial measurements of plasma IL-6 and quantity and depth of sleep, evaluated by polysomnography; and 2) the effects of sleep deprivation on the nyctohemeral pattern of IL-6 secretion. Eight healthy young male volunteers were sampled for 24 h twice, at the baseline state, after a normal night’s sleep and after total overnight sleep deprivation. At the baseline state, IL-6 was secreted in a biphasic circadian pattern with two nadirs at 0800 and 2100 and two zeniths at 1900 and 0500 (P < 0.01). The baseline amount of sleep correlated negatively with the overall daytime secretion of the cytokine (P < 0.05). Also, depth of sleep at baseline correlated negatively with the postdeprivation increase of daytime secretion of IL-6 (P < 0.05). Sleep deprivation changed the temporal pattern of circadian IL-6 secretion but not the overall amount. Indeed, during the postdeprivation period, the mean daytime (0800–2200 h) levels of IL-6 were significantly higher (P < 0.05), whereas the nighttime (2200–0600 h) levels were lower than the predeprivation values. Thus, sleep-deprived subjects had daytime oversecretion and nighttime undersecretion of IL-6; the former might be responsible for their daylong somnolence and fatigue, the latter for the better quality (depth) of their sleep. These data suggest that a good night’s sleep is associated with decreased daytime secretion of IL-6 and a good sense of well-being and that good sleep is associated with decreased exposure of tissues to the proinflammatory and potentially detrimental actions of IL-6. Sleep deprivation increases daytime IL-6 and causes somnolence and fatigue during the next day, whereas postdeprivation decreases nighttime IL-6 and is associated with deeper sleep.

This article has been cited by other articles:

				M. P. Miles, J. M. Andring, S. D. Pearson, L. K. Gordon, C. Kasper, C. M. Depner, and J. R. Kidd Diurnal variation, response to eccentric exercise, and association of inflammatory mediators with muscle damage variables J Appl Physiol, February 1, 2008; 104(2): 451 - 458. [Abstract] [Full Text] [PDF]

				C. Selmi, N. Montano, R. Furlan, C. L. Keen, and M. E. Gershwin Inflammation and Oxidative Stress in Obstructive Sleep Apnea Syndrome Experimental Biology and Medicine, December 1, 2007; 232(11): 1409 - 1413. [Abstract] [Full Text] [PDF]

				M. L. Okun, M. Hall, and M. E. Coussons-Read Sleep Disturbances Increase Interleukin-6 Production During Pregnancy: Implications for Pregnancy Complications Reproductive Sciences, September 1, 2007; 14(6): 560 - 567. [Abstract] [PDF]

				M.-F. O'Connor, S. J. Motivala, E. M. Valladares, R. Olmstead, and M. R. Irwin Sex differences in monocyte expression of IL-6: role of autonomic mechanisms Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R145 - R151. [Abstract] [Full Text] [PDF]

				A. N. Vgontzas, S. Pejovic, E. Zoumakis, H. M. Lin, E. O. Bixler, M. Basta, J. Fang, A. Sarrigiannidis, and G. P. Chrousos 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, January 1, 2007; 292(1): E253 - E261. [Abstract] [Full Text] [PDF]

				R. Wolk and V. K. Somers Sleep Apnoea & Hypertension: Physiological bases for a causal relation: Sleep and the metabolic syndrome Exp Physiol, January 1, 2007; 92(1): 67 - 78. [Abstract] [Full Text] [PDF]

				S. Dimitrov, T. Lange, C. Benedict, M. A. Nowell, S. A. Jones, J. Scheller, S. Rose-John, and J. Born Sleep enhances IL-6 trans-signaling in humans FASEB J, October 1, 2006; 20(12): 2174 - 2176. [Abstract] [Full Text] [PDF]

				M. R. Irwin, M. Wang, C. O. Campomayor, A. Collado-Hidalgo, and S. Cole Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med, September 18, 2006; 166(16): 1756 - 1762. [Abstract] [Full Text] [PDF]

				M. G. Perry, L. Richards, M. S. Harbuz, D. S. Jessop, and J. R. Kirwan Sequential synovial fluid sampling suggests plasma and synovial fluid IL-6 vary independently in rheumatoid arthritis Rheumatology, February 1, 2006; 45(2): 229 - 230. [Full Text] [PDF]

				E. M. Friedman, M. S. Hayney, G. D. Love, H. L. Urry, M. A. Rosenkranz, R. J. Davidson, B. H. Singer, and C. D. Ryff Social relationships, sleep quality, and interleukin-6 in aging women PNAS, December 20, 2005; 102(51): 18757 - 18762. [Abstract] [Full Text] [PDF]

				S. Alesci, P. E. Martinez, S. Kelkar, I. Ilias, D. S. Ronsaville, S. J. Listwak, A. R. Ayala, J. Licinio, H. K. Gold, M. A. Kling, et al. Major Depression Is Associated with Significant Diurnal Elevations in Plasma Interleukin-6 Levels, a Shift of Its Circadian Rhythm, and Loss of Physiological Complexity in Its Secretion: Clinical Implications J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2522 - 2530. [Abstract] [Full Text] [PDF]

				S. J. Motivala, A. Sarfatti, L. Olmos, and M. R. Irwin Inflammatory Markers and Sleep Disturbance in Major Depression Psychosom Med, March 1, 2005; 67(2): 187 - 194. [Abstract] [Full Text] [PDF]

				M. Hamer, D. Wolvers, and R. Albers Using Stress Models to Evaluate Immuno-Modulating Effects of Nutritional Intervention in Healthy Individuals J. Am. Coll. Nutr., December 1, 2004; 23(6): 637 - 646. [Abstract] [Full Text] [PDF]

				A. N. Vgontzas, E. Zoumakis, H.-M. Lin, E. O. Bixler, G. Trakada, and G. P. Chrousos Marked Decrease in Sleepiness in Patients with Sleep Apnea by Etanercept, a Tumor Necrosis Factor-{alpha} Antagonist J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4409 - 4413. [Abstract] [Full Text] [PDF]

				A. N. Vgontzas, E. Zoumakis, E. O. Bixler, H.-M. Lin, H. Follett, A. Kales, and G. P. Chrousos Adverse Effects of Modest Sleep Restriction on Sleepiness, Performance, and Inflammatory Cytokines J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2119 - 2126. [Abstract] [Full Text] [PDF]

				H. K. Meier-Ewert, P. M. Ridker, N. Rifai, M. M. Regan, N. J. Price, D. F. Dinges, and J. M. Mullington Effect of sleep loss on C-Reactive protein, an inflammatory marker of cardiovascular risk J. Am. Coll. Cardiol., February 18, 2004; 43(4): 678 - 683. [Abstract] [Full Text] [PDF]

				A. S. M. Shamsuzzaman, B. J. Gersh, and V. K. Somers Obstructive Sleep Apnea: Implications for Cardiac and Vascular Disease JAMA, October 8, 2003; 290(14): 1906 - 1914. [Abstract] [Full Text] [PDF]

				K.-i. Inoue, H. Takano, T. Yoshikawa, G. E. Carpagnano, and P. J. Barnes Interleukin-6, Obstructive Sleep Apnea, and Obesity Chest, October 1, 2003; 124(4): 1621 - 1623. [Full Text] [PDF]

				J. K. Kiecolt-Glaser, K. J. Preacher, R. C. MacCallum, C. Atkinson, W. B. Malarkey, and R. Glaser Chronic stress and age-related increases in the proinflammatory cytokine IL-6 PNAS, July 22, 2003; 100(15): 9090 - 9095. [Abstract] [Full Text] [PDF]

				A. N. Vgontzas, M. Zoumakis, E. O. Bixler, H.-M. Lin, P. Prolo, A. Vela-Bueno, A. Kales, and G. P. Chrousos 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., May 1, 2003; 88(5): 2087 - 2095. [Abstract] [Full Text] [PDF]

				J. B. Dixon, L. M. Schachter, and P. E. O'Brien Predicting Sleep Apnea and Excessive Day Sleepiness in the Severely Obese: Indicators for Polysomnography Chest, April 1, 2003; 123(4): 1134 - 1141. [Abstract] [Full Text] [PDF]

				T. Yokoe, K. Minoguchi, H. Matsuo, N. Oda, H. Minoguchi, G. Yoshino, T. Hirano, and M. Adachi Elevated Levels of C-Reactive Protein and Interleukin-6 in Patients With Obstructive Sleep Apnea Syndrome Are Decreased by Nasal Continuous Positive Airway Pressure Circulation, March 4, 2003; 107(8): 1129 - 1134. [Abstract] [Full Text] [PDF]

				L. Redwine, J. Dang, M. Hall, and M. Irwin Disordered Sleep, Nocturnal Cytokines, and Immunity in Alcoholics Psychosom Med, January 1, 2003; 65(1): 75 - 85. [Abstract] [Full Text] [PDF]

				G. E. Carpagnano, S. A. Kharitonov, O. Resta, M. P. Foschino-Barbaro, E. Gramiccioni, and P. J. Barnes Increased 8-Isoprostane and Interleukin-6 in Breath Condensate of Obstructive Sleep Apnea Patients Chest, October 1, 2002; 122(4): 1162 - 1167. [Abstract] [Full Text] [PDF]

				A. S.M. Shamsuzzaman, M. Winnicki, P. Lanfranchi, R. Wolk, T. Kara, V. Accurso, and V. K. Somers Elevated C-Reactive Protein in Patients With Obstructive Sleep Apnea Circulation, May 28, 2002; 105(21): 2462 - 2464. [Abstract] [Full Text] [PDF]

				M. A Vickers, F. R Green, C. Terry, B. M Mayosi, C. Julier, M. Lathrop, P. J Ratcliffe, H. C Watkins, and B. Keavney Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein Cardiovasc Res, March 1, 2002; 53(4): 1029 - 1034. [Abstract] [Full Text] [PDF]

				B Hilt, T Qvenild, J Holme, K Svendsen, and B Ulvestad Increase in interleukin-6 and fibrinogen after exposure to dust in tunnel construction workers Occup. Environ. Med., January 1, 2002; 59(1): 9 - 12. [Abstract] [Full Text] [PDF]

				H. K. Meier-Ewert, P. M. Ridker, N. Rifai, N. Price, D. F. Dinges, and J. M. Mullington Absence of Diurnal Variation of C-Reactive Protein Concentrations in Healthy Human Subjects Clin. Chem., March 1, 2001; 47(3): 426 - 430. [Abstract] [Full Text] [PDF]

				L. Redwine, R. L. Hauger, J. C. Gillin, and M. Irwin Effects of Sleep and Sleep Deprivation on Interleukin-6, Growth Hormone, Cortisol, and Melatonin Levels in Humans J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3597 - 3603. [Abstract] [Full Text]

				A. Johansson, K. Carlström, B. Ahrén, K. Cederquist, E. Krylborg, H. Forsberg, and T. Olsson Abnormal Cytokine and Adrenocortical Hormone Regulation in Myotonic Dystrophy J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3169 - 3176. [Abstract] [Full Text]

				A. N. Vgontzas, E. O. Bixler, D. A. Papanicolaou, G. P. Chrousos, B. R. Bistrian, L. Khaodhiar, M. Visser, and T. B. Harris Chronic Systemic Inflammation in Overweight and Obese Adults JAMA, May 3, 2000; 283(17): 2235 - 2236. [Full Text] [PDF]

				D. A. Papanicolaou Interleukin-6: The Endocrine Cytokine J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1331 - 1333. [Full Text]