Effects of sleep deprivation on nocturnal cytokine concentrations in depressed patients and healthy control subjects.

Previous studies have reported alterations of cytokine and cytokine-receptor concentrations in psychiatric patient populations, including patients with major depressive disorder (MDD). However, study results are conflicting, and possible causes for these abnormalities are unknown. Since sleep deprivation may induce a rapid improvement of mood in depressed patients, the authors investigated the impact of total sleep deprivation (TSD) for one night, and subsequent recovery sleep, on nocturnal concentrations of interleukin-6 (IL-6), interleukin-1-receptor antagonist (IL-1RA), and soluble IL-2 receptor (sIL-2R) in 15 unmedicated patients with MDD and 16 healthy volunteers. Whereas IL-6 levels normalized again during the recovery night in depressed patients, they were still elevated in control subjects. Serum levels of IL-1RA were higher in depressed patients than in controls, but were not affected by TSD. During recovery sleep, IL-1RA levels increased as compared with the preceding TSD night only in controls. Responders (N=8) differed from nonresponders (N=7) to TSD with regard to IL-1RA, which increased significantly during TSD in responders only. Sleep deprivation therefore seems to significantly affect cytokine levels in both depressed patients and healthy subjects, but does so in different ways. Sleep disturbances in depressed patients could account for the increased levels of cytokines found in these patients in several previous studies. The interaction between antidepressant effects of TSD and alterations of cytokines warrants further investigation.

[1]  R. Carasso,et al.  REM sleep deprivation in rats results in inflammation and interleukin-17 elevation. , 2009, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[2]  S. Keinänen-Kiukaanniemi,et al.  Depressive symptomatology is associated with decreased interleukin-1 beta and increased interleukin-1 receptor antagonist levels in males , 2009, Psychiatry Research.

[3]  Charles L. Raison,et al.  Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression , 2009, Biological Psychiatry.

[4]  J. Suls,et al.  Associations of Depression With C-Reactive Protein, IL-1, and IL-6: A Meta-Analysis , 2009, Psychosomatic medicine.

[5]  Andrew H. Miller.  Mechanisms of cytokine-induced behavioral changes: Psychoneuroimmunology at the translational interface , 2009, Brain, Behavior, and Immunity.

[6]  H. Calil,et al.  Inflammatory aspects of depression. , 2008, Inflammation & allergy drug targets.

[7]  G. Kostopanagiotou,et al.  Effect of exogenous catecholamines on tumor necrosis factor alpha, interleukin-6, interleukin-10 and beta-endorphin levels following severe trauma. , 2008, Vascular pharmacology.

[8]  E. Bixler,et al.  Hypothalamic-pituitary-adrenal axis activity in obese men with and without sleep apnea: effects of continuous positive airway pressure therapy. , 2007, The Journal of clinical endocrinology and metabolism.

[9]  Kenneth P. Wright,et al.  The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults , 2007, Brain, Behavior, and Immunity.

[10]  M. Irwin,et al.  Depressive disorders and immunity: 20 years of progress and discovery , 2007, Brain, Behavior, and Immunity.

[11]  K. Matthews,et al.  Depressive symptoms and production of proinflammatory cytokines by peripheral blood mononuclear cells stimulated in vitro , 2007, Brain, Behavior, and Immunity.

[12]  M. Irwin,et al.  Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. , 2006, Archives of internal medicine.

[13]  T. Reistad,et al.  Seven days’ around the clock exhaustive physical exertion combined with energy depletion and sleep deprivation primes circulating leukocytes , 2006, European Journal of Applied Physiology.

[14]  A. Harris,et al.  Cytokine Dysregulation, Inflammation and Well-Being , 2005, Neuroimmunomodulation.

[15]  Carol A Everson,et al.  Clinical assessment of blood leukocytes, serum cytokines, and serum immunoglobulins as responses to sleep deprivation in laboratory rats. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[16]  E. Bixler,et al.  IL-6 and Its Circadian Secretion in Humans , 2005, Neuroimmunomodulation.

[17]  M. Hüll,et al.  Serotonin via 5‐HT7 receptors activates p38 mitogen‐activated protein kinase and protein kinase C ɛ resulting in interleukin‐6 synthesis in human U373 MG astrocytoma cells , 2005, Journal of neurochemistry.

[18]  J. O'Callaghan,et al.  Depression, cytokines, and glial function. , 2005, Metabolism: clinical and experimental.

[19]  E. Bixler,et al.  Marked decrease in sleepiness in patients with sleep apnea by etanercept, a tumor necrosis factor-alpha antagonist. , 2004, The Journal of clinical endocrinology and metabolism.

[20]  C. Kirschbaum,et al.  Impact of sleep deprivation and subsequent recovery sleep on cortisol in unmedicated depressed patients. , 2004, The American journal of psychiatry.

[21]  E. Bixler,et al.  Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines. , 2004, The Journal of clinical endocrinology and metabolism.

[22]  J. Manuel,et al.  Sleep-deprived mice show altered cytokine production manifest by perturbations in serum IL-1ra, TNFa, and IL-6 levels , 2003, Brain, Behavior, and Immunity.

[23]  E. Bixler,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. , 2003, The Journal of clinical endocrinology and metabolism.

[24]  T. Pollmächer,et al.  Diurnal variations of interleukin-6 plasma levels are confounded by blood drawing procedures , 2002, Psychoneuroendocrinology.

[25]  E. Smeraldi,et al.  Interleukine-6 serum levels correlate with response to antidepressant sleep deprivation and sleep phase advance , 2002, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[26]  T. Pollmächer,et al.  Low levels of circulating inflammatory cytokines—Do they affect human brain functions? , 2002, Brain, Behavior, and Immunity.

[27]  K. Nas,et al.  Cytokines and depression in cases with fibromyalgia. , 2002, The Journal of rheumatology.

[28]  E. Bosmans,et al.  Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis , 2001, European Neuropsychopharmacology.

[29]  R. Lam,et al.  Immune-inflammatory markers in patients with seasonal affective disorder: effects of light therapy. , 2001, Journal of affective disorders.

[30]  S. Yamawaki,et al.  Plasma Concentrations of Interleukin-1β, Interleukin-6, Soluble Interleukin-2 Receptor and Tumor Necrosis Factor α of Depressed Patients in Japan , 2001, Neuropsychobiology.

[31]  W. Scherbaum,et al.  The role of interleukin‐6 in the human adrenal gland , 2000, European journal of clinical investigation.

[32]  M Irwin,et al.  Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans. , 2000, The Journal of clinical endocrinology and metabolism.

[33]  H. Vedder,et al.  Cytokine Production and Treatment Response in Major Depressive Disorder , 2000, Neuropsychopharmacology.

[34]  B. Leonard.  Stress, Depression and the Activation of the Immune System , 2000, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[35]  T. Pollmächer,et al.  Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. , 1999, Journal of psychiatric research.

[36]  Anna Wirz-Justice,et al.  Sleep deprivation in depression: what do we know, where do we go? , 1999, Biological Psychiatry.

[37]  D. Papanicolaou,et al.  Circadian interleukin-6 secretion and quantity and depth of sleep. , 1999, The Journal of clinical endocrinology and metabolism.

[38]  J. Born,et al.  Acute effects of recombinant human interleukin-6 on endocrine and central nervous sleep functions in healthy men. , 1998, The Journal of clinical endocrinology and metabolism.

[39]  S. Kanba,et al.  Aberrant interleukin-2 receptor-mediated blastoformation of peripheral blood lymphocytes in a severe major depressive episode , 1998, Psychological Medicine.

[40]  Fritz Hohagen,et al.  Impact of Experimentally Induced Serotonin Deficiency by Tryptophan Depletion on Sleep EEG in Healthy Subjects , 1998, Neuropsychopharmacology.

[41]  E. Bosmans,et al.  Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. , 1997, Cytokine.

[42]  J. Born,et al.  Effects of sleep and circadian rhythm on human circulating immune cells. , 1997, Journal of immunology.

[43]  E. Bosmans,et al.  Indicators of immune activation in major depression , 1996, Psychiatry Research.

[44]  D. Papanicolaou,et al.  Exercise stimulates interleukin-6 secretion: inhibition by glucocorticoids and correlation with catecholamines. , 1996, The American journal of physiology.

[45]  J. Bauer,et al.  Interleukin‐1β Uses Common and Distinct Signaling Pathways for Induction of the Interleukin‐6 and Tumor Necrosis Factor α Genes in the Human Astrocytoma Cell Line U373 , 1996 .

[46]  B. Rabin,et al.  Interleukin 6 modulates interleukin-1-and stress-induced activation of the hypothalamic-pituitary-adrenal axis in male rats. , 1996, Neuroendocrinology.

[47]  A. BØyum,et al.  The Effect of Strenuous Exercise, Calorie Deficiency and Sleep Deprivation on White Blood Cells, Plasma Immunoglobulins and Cytokines , 1996, Scandinavian journal of immunology.

[48]  A. Turnbull,et al.  Regulation of the HPA Axis by Cytokines , 1995, Brain, Behavior, and Immunity.

[49]  H. Meltzer,et al.  Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. , 1995, Journal of affective disorders.

[50]  L. Aarden,et al.  Differential induction of interleukin-6 production by monocytes, endothelial cells and smooth muscle cells. , 1991, Progress in clinical and biological research.

[51]  H. Moldofsky,et al.  Effects of sleep deprivation on human immune functions , 1989, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[52]  T. Hirano,et al.  Regulation of interleukin-6 expression in cultured human blood monocytes and monocyte-derived macrophages , 1988 .

[53]  M. Hamilton.  A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[54]  J. Bauer,et al.  Interleukin-6-(IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission , 2008, European Archives of Psychiatry and Clinical Neuroscience.

[55]  B. Feige,et al.  Are there gender differences in objective and subjective sleep measures? A study of insomniacs and healthy controls , 2003, Depression and anxiety.

[56]  S. Yamawaki,et al.  Plasma concentrations of interleukin-1beta, interleukin-6, soluble interleukin-2 receptor and tumor necrosis factor alpha of depressed patients in Japan. , 2001, Neuropsychobiology.

[57]  D F Dinges,et al.  Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight. , 2001, The Journal of allergy and clinical immunology.

[58]  J. Bauer,et al.  Interleukin-1 beta uses common and distinct signaling pathways for induction of the interleukin-6 and tumor necrosis factor alpha genes in the human astrocytoma cell line U373. , 1996, Journal of neurochemistry.

[59]  N. Rothwell,et al.  Cytokines and their receptors in the central nervous system: physiology, pharmacology, and pathology. , 1996, Pharmacology & therapeutics.

[60]  D. Dinges,et al.  Sleep deprivation and human immune function. , 1995, Advances in neuroimmunology.

[61]  H. Meltzer,et al.  Immunoendocrine aspects of major depression. Relationships between plasma interleukin-6 and soluble interleukin-2 receptor, prolactin and cortisol. , 1995, European archives of psychiatry and clinical neuroscience.

[62]  J. Wu,et al.  The biological basis of an antidepressant response to sleep deprivation and relapse: review and hypothesis. , 1990, The American journal of psychiatry.