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Role of Pro-Inflammatory Cytokines in Sleep Disorders

  • Chapter
Neuroendocrine Correlates of Sleep/Wakefulness

Abstract

This chapter is designed to characterize how pro-inflammatory cytokines are involved in sleep regulation. Basic observations demonstrate that cytokines have a physiological role in sleep regulation with both somnogenic and inhibitory effects depending on the cytokine, dose and diurnal and/or circadian phase. These basic mechanisms have not yet been translated into clinical applications, although they have tremendous implications for answering why sleep is disturbed in so many individuals, and may eventually provide effective treatment. Yet, relationships between cytokine expression and sleep in healthy and insomniac populations at different ages are a current topic of investigation in several laboratories. Circadian expressions of interleukin (IL)-6, tumor necrosis factor α (TNF), adrenocorticotropic hormone (ACTH) and cortisol have been evaluated in various studies. Generally speaking, older individuals do not show increased daytime sleepiness when compared to controls, but display more daytime fatigue in all studies

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References

  1. Kales and Kales, 1984 Kales A, Kales JD. Evaluation and treatment of insomnia. New York: Oxford University Press 1984.

    Google Scholar 

  2. Gold PW, Chrousos GP. The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences. Proc. Assoc. Am. Phys. 1999 111: 22–34.

    Article  PubMed  CAS  Google Scholar 

  3. Chrousos GA, Kattah JC, Beck RW, Cleary PA and the Optic Neuritis Study Group. Side effects of glucocorticoid treatment. JAMA 1993 269:2110–2112.

    Article  PubMed  CAS  Google Scholar 

  4. Opp M, Obal Jr F, Kreuger JM Corticotropin-releasing factor attenuates interleukin 1-induced sleep and fever in rabbits. Am J Physiol 1989 257:R528–R535.

    PubMed  CAS  Google Scholar 

  5. Chiappelli F, Abanomy A, Hodgson D, Mazey KA, Messadi DV, Mito RS, Nishimura I, Spigleman, I.. Clinical, experimental and translational psychoneuroimmunology research models in oral biology and medicine. In Psychoneuroimmunology, III; Robert Ader, Robert Cohen and David Felten eds, Academic Press, Chapter 64, 2001 pp. 645–70.

    Google Scholar 

  6. Chiappelli F, Prolo P, Cajulis E, Harper S, Sunga E, Concepcion E. Consciousness, emotional self-regulation, and the psychosomatic network: Relevance to Oral Biology and Medicine. In Consciousness, Emotional Self-regulation and the Brain; M. Beauregard, Ed. Advances in Consciousness Research, John Benjamins Publishing Company, Chapter 9 2004 pp. 253–274.

    Google Scholar 

  7. Chiappelli F, Cajulis O. Psychobiological Views on “Stress-Related Oral Ulcers”. Quintessence Int. 2004; 35: 233–237.

    Google Scholar 

  8. Prolo P, Chiappelli F, Fiorucci A, Dovio A, Sartori ML, Angeli A. Psychoneuroimmunology: new avenues of research for the 21st century Ann NY Acad Sci 2002 966: 400–408.

    Article  PubMed  CAS  Google Scholar 

  9. Vgontzas AN, Papanicolaou DA, Bixler EO, Lotsikas A, Zachman K, Kales A, Wong M-L, Licinio J, Prolo P, PW Gold PW, Hermida RC, Mastorakos G, Chrousos GP: Circadian interleukin-6 secretion and quantity and depth of sleep. Journal of Clinical Endocrinology & Metabolism 1999 84:2603–2607.

    Article  CAS  Google Scholar 

  10. Kunz-Ebrecht SR, Mohamed-Ali V, Feldman PJ, Kirschbaum C, Steptoe A. Cortisol responses to mild psychological stress are inversely associated with proinflammatory cytokines. Brain Behav Imm 2003 17:373–383.

    Article  CAS  Google Scholar 

  11. Steptoe A, Willemsen G, Owen N, Flower L, Mohamed-Ali V. Acute mental stress elicits delayed increases in circulating inflammatory cytokine levels. Clin Sci (Lond). 2001 101:185–192.

    Article  CAS  Google Scholar 

  12. Vgontzas AN, Bixler EO, Lin H-M, Prolo P, Mastorakos G, Vela-Bueno A, Kales A, Chrousos GP 2001 Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. J Clin Endocrinol Metab 2001 86:3787–3794.

    Article  PubMed  CAS  Google Scholar 

  13. Irwin M. Effects of sleep and sleep loss on immunity and cytokines. Brain Behav Immun. 2002 16:503–512.

    Article  PubMed  CAS  Google Scholar 

  14. Drize N, Chertkov J, Samoilina N, Zander A. Effect of cytokine treatment (granulocyte colony-stimulating factor and stem cell factor) on hematopoiesis and the circulating pool of hematopoietic stem cells in mice. Exp Hematol. 1996; 24:816–822.

    PubMed  CAS  Google Scholar 

  15. McNiece IK, Briddell RA, Hartley CA, Smith KA, Andrews RG. Stem cell factor enhances in vivo effects of granulocyte colony stimulating factor for stimulating mobilization of peripheral blood progenitor cells. Stem Cells. 1993; 11Suppl 2:36–41.

    PubMed  CAS  Google Scholar 

  16. Weber C, Arck P, Mazurek B, Klapp BF. Impact of a relaxation training on psychometric and immunologic parameters in tinnitus sufferers. J Psychosom Res. 2002; 52:29–33.

    Article  PubMed  Google Scholar 

  17. Nemunaitis J, Singer JW, Buckner CD, Mori T, Laponi J, Hill R, Storb R, Sullivan KM, Hansen JA, Appelbaum FR. Long-term follow-up of patients who received recombinant human granulocyte-macrophage colony stimulating factor after autologous bone marrow transplantation for lymphoid malignancy. Bone Marrow Transplant. 1991;7:49–52

    PubMed  CAS  Google Scholar 

  18. Ackerman KD, Martino M, Heyman R, Moyna NM, Rabin BS. Stressor-induced alteration of cytokine production in multiple production sclerosis patients and controls. Psychosom Med 1998 60: 484–491.

    PubMed  CAS  Google Scholar 

  19. Arck PC, Rose M, Hertwig K, Hagen E, Hildebrandt M, Klapp BF. Stress and immune mediators in miscarriage. Hum Reprod 2001 16: 1505–1511.

    Article  PubMed  CAS  Google Scholar 

  20. Hauser P, Soler R, Reed S, Kane R, Gulati M, Khosla J, Kling MA, Valentine AD, Meyers CA. Prophylactic treatment of depression induced by interferon-alpha. Psychosomatics. 2000;41:439–441.

    Article  PubMed  CAS  Google Scholar 

  21. Tilg H, Vogel W, Dinarello CA. Interferon-alpha induces circulating tumor necrosis factor receptor p55 in humans. Blood. 1995; 85:433–435.

    PubMed  CAS  Google Scholar 

  22. Carlson LE, Speca M, Patel KD, Goodey E. Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate (DHEAS) and melatonin in breast and prostate cancer outpatients. Psychoneuroendocrinology 2004 29:448–474.

    Article  PubMed  CAS  Google Scholar 

  23. Reibel DK, Greeson JM, Brainard GC, Rosenzweig S. Mindfulness-based stress reduction and health-related quality of life in a heterogeneous patient population. Gen Hosp Psychiatry. 2001 23:183–192.

    Article  PubMed  CAS  Google Scholar 

  24. Solberg EE, Halvorsen R, Sundgot-Borgen J, Ingjer F, Holen A. Meditation: a modulator of the immune response to physical stress? A brief report. Br J Sports Med. 1995 29:255–257.

    Article  PubMed  CAS  Google Scholar 

  25. Taylor DN. Effects of a behavioral stress-management program on anxiety, mood, self-esteem, and T-cell count in HIV positive men. Psychol Rep. 1995 76:451–457.

    PubMed  CAS  Google Scholar 

  26. Petry LJ, Weems LB 2nd, Livingstone JN 2nd. Relationship of stress, distress, and the immunologic response to a recombinant hepatitis B vaccine. J Fam Pract. 1991 32:481–486.

    PubMed  CAS  Google Scholar 

  27. Buijs RM. The anatomical basis for the expression of circadian rhythms: the efferent projections of the suprachiasmatic nucleus. Prog Brain Res. 1996;111:229–240.

    Article  PubMed  CAS  Google Scholar 

  28. Rosenwasser AM. Alcohol, Antidepressants, and Circadian Rhythms Human and Animal Models 2004 NIAAA Publications http://www.niaaa.nih.gov/publications/arh25-2/126-135.htm

  29. Kodama H, Nakazawa Y, Kotorii T, Nonaka K, Inanaga K, Ohshima M, Tokoyama T. Biorhythm of core temperature in depressive and non-depressive alcoholics. Drug and Alcohol Dependence 1988 21: 1–6.

    Article  PubMed  CAS  Google Scholar 

  30. Imatoh N, Nakazawa Y, Ohshima H, Ishibashi M, Yokoyama T. Circadian rhythm of REM sleep of chronic alcoholics during alcohol withdrawal. Drug and Alcohol Dependence 1986 18:77–85.

    Article  PubMed  CAS  Google Scholar 

  31. Sano H, Suzuki Y, Yazaki R, Tamefusa K, Ohara K, Yokoyama T, Miyasato K, Ohara K. Circadian variation in plasma 5-hydroxyindoleacetic acid level during and after alcohol withdrawal: phase advances in alcoholic patients compared with normal subjects. Acta Psychiatr Scand. 1993;87:291–296.

    Article  PubMed  CAS  Google Scholar 

  32. Sano H, Suzuki Y, Ohara K, Miyasato K, Yokoyama T, Ohara K. Circadian variations in plasma monoamine metabolites level in alcoholic patients: a possible predictor of alcohol withdrawal delirium. Prog Neuropsychopharmacol Biol Psychiatry. 1994;18:741–752.

    Article  PubMed  CAS  Google Scholar 

  33. Iranmanesh A, Veldhuis JD, Johnson ML, Lizarralde G. 24-hour pulsatile and circadian patterns of cortisol secretion in alcoholic men. Journal of Andrology 1989 10: 54–63.

    PubMed  CAS  Google Scholar 

  34. Wong M-L, Kling MA, Munson PJ, Listwak S, Licinio J, Prolo P, Chrousos GP, Oldfield EH, McCann SM, Gold PW: Stress system dysfunction in major depression: Serial cerebrospinal fluid sampling of corticotropin releasing hormone and norepinephrine. Proceedings of the National Academy of Sciences U.S.A. 2000 97; 325–330.

    Article  CAS  Google Scholar 

  35. Fernandez JR, Hermida RC. Inferential statistical method for analysis of nonsinusoidal hybrid time series with unequidistant observations. Chronobiol Int 1998 15:191–204.

    Article  PubMed  CAS  Google Scholar 

  36. Prinz PN, Bailey SL, Woods DL. Sleep impairments in healthy seniors: roles of stress, cortisol, and interleukin-1 beta. Chronobiol Int. 2000;17:391–404.

    Article  PubMed  CAS  Google Scholar 

  37. Ferrari E, Cravello L, Muzzoni B, Casarotti D, Paltro M, Solerte SB, Fioravanti M, Cuzzoni G, Pontiggia B, Magri F Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates. Eur J Endocrinol. 2001 144:319–329.

    Article  PubMed  CAS  Google Scholar 

  38. Van Cauter E, Leproult R, Plat L. Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. JAMA 2000 284:861–868.

    Article  PubMed  Google Scholar 

  39. Luc G, Bard JM, Juhan-Vague I, Ferrieres J, Evans A, Amouyel P, Arveiler D, Fruchart JC, Ducimetiere P. PRIME Study Group. C-reactive protein, interleukin-6, and fibrinogen as predictors of coronary heart disease: the PRIME Study. Arterioscler Thromb Vasc Biol 2003 23:1255–1261.

    Article  PubMed  CAS  Google Scholar 

  40. Singh RB, Kartik C, Otsuka K, Pella D, Pella J. Brain-heart connection and the risk of heart attack. Biomed Pharmacother 2002;56Suppl 2:257s–265s.

    Article  PubMed  Google Scholar 

  41. Vgontzas AN, Zoumakis M, Ebixler EO, Lin HM, Prolo P, Vela-Bueno A Kales A, Chrousos GP. Impaired Nighttime Sleep In Healthy Old Vs. Young Adults is Associated with Elevated Plasma IL-6 and Cortisol Levels: Physiologic and Therapeutic Implications. J Clin Endocrinol Metab 2003 88: 2087–2095.

    Article  PubMed  CAS  Google Scholar 

  42. Pavlov EP, Harman SM, Chrousos GP, Loriaux DL, Blackman MR. Responses of plasma adrenocorticotropin, cortisol, and dehydroepiandrosterone to ovine corticotropin-releasing hormone in healthy aging men. J Clin Endocrinol Metab. 1986;62:767–772.

    Article  PubMed  CAS  Google Scholar 

  43. Van Cauter E, Leproult R, Kupfer DJ. Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol. J Clin Endocrinol Metab. 1996;81:2468–2473.

    Article  PubMed  Google Scholar 

  44. Imagawa S, Yamaguchi Y, Ogawa K, Obara N, Suzuki N, Yamamoto M, Nagasawa T. Interleukin-6 and tumor necrosis factor-alpha in patients with obstructive sleep apnea-hypopnea syndrome. Respiration 2004; 71:24–29.

    Article  PubMed  CAS  Google Scholar 

  45. Irwin M, Rinetti G, Redwine L, Motivala S, Dang J, Ehlers C Nocturnal proin-flammatory cytokine-associated sleep disturbances in abstinent African American alcoholics. Brain Behav Immun. 2004;18:349–360.

    Article  PubMed  CAS  Google Scholar 

  46. Chrousos GP, Gold PW. A healthy body in a healthy mind—and vice versa—the damaging power of “uncontrollable” stress. J Clin Endocrinol Metab. 1998 83:1842–1845.

    Article  PubMed  CAS  Google Scholar 

  47. Gold PW, Wong ML, Chrousos GP, Licinio J. Stress system abnormalities in melancholic and atypical depression: molecular, pathophysiological, and therapeutic implications. Mol Psychiatry. 1996;1:257–264.

    PubMed  CAS  Google Scholar 

  48. Prolo P, Chiappelli F, Cajulis E, Bauer J, Spackman S, Romeo H, Carrozzo M, Gandolfo S, Christensen R. Psychoneuroimmunology in Oral Biology and Medicine: The Model of Oral Lichen Planus. Ann NY Acad Sci 2002 966:429–440.

    Article  PubMed  CAS  Google Scholar 

  49. Prolo P, Licinio J. Molecular neuroendocrinology and its impact on behavior. In: Genes, Behavior, and Health. (C.L. Bolis and J. Licinio eds.) World Health Organization, Geneva, Swizerland 1999 pp. 37–60.

    Google Scholar 

  50. Chilcott LA, Shapiro CM. The socioeconomic impact of insomnia. An overview. Pharmacoeconomics. 1996;10Suppl 1:1–14.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. School of Dentistry Psychoneuroimmunology, University of California, Los Angeles, Los Angeles, CA

    Paolo Prolo, Negoita Negaos & Francesco Chiappelli

  2. Center for Community Health, UCLA Neuropsychiatric Institute, Los Angeles, CA

    Francisco J. Iribarren

Authors
  1. Paolo Prolo
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  2. Francisco J. Iribarren
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  3. Negoita Negaos
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  4. Francesco Chiappelli
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Editor information

Editors and Affiliations

  1. Department of Physiology Faculty of Medicine, University of Buenos Aires, Argentina, Buenos Aires, 1121

    Daniel P. Cardinali

  2. SUNY Downstate Medical Center, Brooklyn, 11203, New York, USA

    S. R. Pandi-Perumal

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Prolo, P., Iribarren, F.J., Negaos, N., Chiappelli, F. (2006). Role of Pro-Inflammatory Cytokines in Sleep Disorders. In: Cardinali, D.P., Pandi-Perumal, S.R. (eds) Neuroendocrine Correlates of Sleep/Wakefulness. Springer, Boston, MA. https://doi.org/10.1007/0-387-23692-9_29

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