Stress-associated immune modulation: relevance to viral infections and chronic fatigue syndrome.

The frequent association of an active viral infection with the symptoms of CFS led researchers to hypothesize that chronic fatigue syndrome (CFS) is induced by a virus. Results of these studies indicated that despite clinical support for this hypothesis, there were no clear data linking viruses to CFS. In this overview, we will explore the interrelation of the immune, endocrine, and central nervous systems, and the possibility that stress and/or the reactivation/replication of a latent virus (such as Epstein Barr virus) could modulate the immune system to induce CFS. Relevant research conducted in the developing field of psychoneuroimmunology will be reviewed, with a particular focus on cytokine synthesis, natural killer (NK) cell activity, and T-lymphocyte function, as they relate to CFS.

[1]  J. Chen,et al.  Frequency and levels of antibodies to Epstein-Barr virus-specific DNase are elevated in patients with nasopharyngeal carcinoma. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Andrew P. Smith,et al.  Psychological stress and susceptibility to the common cold. , 1991, The New England journal of medicine.

[3]  J. Stout,et al.  Stress depresses interferon production by leukocytes concomitant with a decrease in natural killer cell activity. , 1986, Behavioral neuroscience.

[4]  J. Kiecolt-Glaser,et al.  Stress and the memory T-cell response to the Epstein-Barr virus in healthy medical students. , 1993, Health psychology : official journal of the Division of Health Psychology, American Psychological Association.

[5]  W. Malarkey,et al.  Slowing of wound healing by psychological stress , 1995, The Lancet.

[6]  J. Sheridan,et al.  Stress-induced suppression of herpes simplex virus (HSV)-specific cytotoxic T lymphocyte and natural killer cell activity and enhancement of acute pathogenesis following local HSV infection , 1991, Brain, Behavior, and Immunity.

[7]  A. Komaroff,et al.  Prevalence of IgM antibodies to human herpesvirus 6 early antigen (p41/38) in patients with chronic fatigue syndrome. , 1995, The Journal of infectious diseases.

[8]  J. Kiecolt-Glaser,et al.  Changes in Epstein-Barr Virus Antibody Titers Associated with Aging , 1985, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[9]  R. Ader,et al.  Psychoneuroimmunology, 2nd ed. , 1991 .

[10]  R. S. Tan,et al.  Demonstration of Epstein-Barr virus-specific DNA polymerase in chemically induced Raji cells and its antibody in serum from patients with nasopharyngeal carcinoma. , 1986, Cancer research.

[11]  W. Malarkey,et al.  Stress‐induced modulation of the immune response to recombinant hepatitis B vaccine. , 1992, Psychosomatic medicine.

[12]  J. Kiecolt-Glaser,et al.  Chronic stress modulates the virus-specific immune response to latent herpes simplex virus Type 1 , 1997, Annals of behavioral medicine : a publication of the Society of Behavioral Medicine.

[13]  R. MacCallum,et al.  Hormonal modulation of Epstein-Barr virus replication. , 1995, Neuroendocrinology.

[14]  J. Stout,et al.  Stress-related impairments in cellular immunity , 1985, Psychiatry Research.

[15]  Rodney W. Johnson,et al.  Role of corticosterone in the behavioral effects of central interleukin-1β , 1997, Physiology & Behavior.

[16]  W. Henle,et al.  Characteristic T cell dysfunction in patients with chronic active Epstein-Barr virus infection (chronic infectious mononucleosis). , 1985, Journal of immunology.

[17]  G. Fricchione,et al.  The stress response and autoimmunoregulation. , 1994, Advances in neuroimmunology.

[18]  E. Hoover,et al.  Immunosuppressive properties of a virion polypeptide, a 15,000-dalton protein, from feline leukemia virus. , 1979, Cancer research.

[19]  S. Maier,et al.  Cytokine-to-brain communication: a review & analysis of alternative mechanisms. , 1995, Life sciences.

[20]  Melinda Beck,et al.  Stress-related immune suppression: Health implications , 1987, Brain, Behavior, and Immunity.

[21]  R. Davey,et al.  Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. , 1985, Annals of internal medicine.

[22]  F. Rapp,et al.  Studies of an Epstein-Barr virus-induced DNA polymerase. , 1977, Virology.

[23]  J. Phair,et al.  Serum neopterin and interleukin-6 levels in chronic fatigue syndrome. , 1990, The Journal of infectious diseases.

[24]  J. Sheridan,et al.  Chronic stress alters the immune response to influenza virus vaccine in older adults. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[25]  S. Gravenstein,et al.  Efficacy of an Influenza Hemagglutinin‐Diphtheria Toxoid Conjugate Vaccine in Elderly Nursing Home Subjects During an Influenza Outbreak , 1994, Journal of the American Geriatrics Society.

[26]  S. Shafran The chronic fatigue syndrome. , 1991, The American journal of medicine.

[27]  A. Vingerhoets,et al.  Influence of perceived psychological stress and distress on antibody response to low dose rDNA hepatitis B vaccine. , 1993, Journal of psychosomatic research.

[28]  J. Sheridan,et al.  The effect of restraint stress on the kinetics, magnitude, and isotype of the humoral immune response to influenza virus infection , 1991, Brain, Behavior, and Immunity.

[29]  J L Sullivan,et al.  Frequency of 'chronic active Epstein-Barr virus infection' in a general medical practice. , 1987, JAMA.

[30]  J. Mintz,et al.  Herpes simplex virus and moods: a longitudinal study. , 1976, Journal of psychosomatic research.

[31]  R. Glaser,et al.  Stress-associated modulation of proto-oncogene expression in human peripheral blood leukocytes. , 1993, Behavioral neuroscience.

[32]  W. Henle,et al.  Antibodies to the R component of Epstein-Barr virus-induced early antigens in Burkitt's lymphoma exceeding in titer antibodies to Epstein-Barr capsid antigen. , 1977, Journal of the National Cancer Institute.

[33]  U. Tirelli,et al.  Immunological abnormalities in chronic fatigue syndrome , 1995 .

[34]  M. Minkler,et al.  Social support and health. , 1982, Patient education newsletter.

[35]  James F. Jones,et al.  Stress-related activation of Epstein-Barr virus , 1991, Brain, Behavior, and Immunity.

[36]  J. Joncas,et al.  The effect of hydrocortisone and bromodeoxyuridine (BUdR) on the Epstein-Barr herpes virus in human lymphoblastoid cell lines. , 1974, Revue canadienne de biologie.

[37]  C E Speicher,et al.  Chronic stress and immunity in family caregivers of Alzheimer's disease victims. , 1987, Psychosomatic medicine.

[38]  J. Chen,et al.  Studies on the activity of DNase associated with the replication of the Epstein-Barr virus. , 1980, Virology.

[39]  S. Adler,et al.  Immunologic evidence for frequent age-related cytomegalovirus reactivation in seropositive immunocompetent individuals. , 1989, The Journal of infectious diseases.

[40]  M. Caligiuri,et al.  Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. , 1987, Journal of immunology.

[41]  S. Schwartz,et al.  Immunoregulatory activities of human immunodeficiency virus (HIV) proteins: effect of HIV recombinant and synthetic peptides on immunoglobulin synthesis and proliferative responses by normal lymphocytes. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[42]  I. Magrath,et al.  Enhancement of Epstein-Barr virus replication in producer cell lines by a combination of low temperature and corticosteroids. , 1979, Virology.

[43]  I. Hickie,et al.  The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. , 1994, Annals of internal medicine.

[44]  M. Fletcher,et al.  Immunologic abnormalities in chronic fatigue syndrome , 1990, Journal of clinical microbiology.

[45]  P. Pinsky,et al.  A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause? , 1987, JAMA.

[46]  T. F. Smith,et al.  Chronic fatigue syndrome and the diagnostic utility of antibody to Epstein-Barr virus early antigen. , 1988, JAMA.

[47]  G. Klein,et al.  Antibodies to early Epstein-Barr virus-induced antigens in Burkitt's lymphoma. , 1971, Journal of the National Cancer Institute.

[48]  J. Kiecolt-Glaser,et al.  Psychological stress and phorbol ester inhibition of radiation-induced apoptosis in human peripheral blood leukocytes , 1990, Psychiatry Research.

[49]  B. Natelson,et al.  High titers of anti‐epstein‐barr virus DNA polymerase are found in patients with severe fatiguing illness , 1994, Journal of medical virology.

[50]  J. Kiecolt-Glaser,et al.  Psychosocial Modifiers of Immunocompetence in Medical Students , 1984, Psychosomatic medicine.

[51]  G. Krueger,et al.  Clinical correlates of infection with human herpesvirus-6. , 1994, In vivo.

[52]  J. Kiecolt-Glaser,et al.  Psychosocial Modulation of Cytokine-Induced Natural Killer Cell Activity in Older Adults , 1996, Psychosomatic medicine.

[53]  P. Mirandola,et al.  Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome , 1995, Journal of clinical microbiology.

[54]  A. Komaroff,et al.  Viral serologies in patients with chronic fatigue and chronic fatigue syndrome , 1996, Journal of medical virology.

[55]  J. Sheridan,et al.  Growth hormone secretion by human peripheral blood mononuclear cells detected by an enzyme-linked immunoplaque assay. , 1993, The Journal of clinical endocrinology and metabolism.

[56]  Ian Hickie,et al.  The Chronic Fatigue Syndrome: A Comprehensive Approach to Its Definition and Study , 1994, Annals of Internal Medicine.

[57]  H. Weingarten Cytokines and food intake: The relevance of the immune system to the student of ingestive behavior , 1996, Neuroscience & Biobehavioral Reviews.

[58]  R. Glaser,et al.  Psychological stress-induced modulation of interleukin 2 receptor gene expression and interleukin 2 production in peripheral blood leukocytes. , 1990, Archives of general psychiatry.

[59]  James F. Jones,et al.  Evidence for Active Epstein-Barr Virus Infection in Patients with Persistent, Unexplained Illnesses: Elevated Anti-Early Antigen Antibodies , 1985 .

[60]  P. Black Immune system-central nervous system interactions: effect and immunomodulatory consequences of immune system mediators on the brain , 1994, Antimicrobial Agents and Chemotherapy.

[61]  A. Komaroff,et al.  Symptoms and signs of chronic fatigue syndrome. , 1991, Reviews of infectious diseases.

[62]  W. Katon,et al.  Chronic fatigue. A prospective clinical and virologic study. , 1990, JAMA.

[63]  J. Kiecolt-Glaser,et al.  Chronic stress, social support, and persistent alterations in the natural killer cell response to cytokines in older adults. , 1994, Health psychology : official journal of the Division of Health Psychology, American Psychological Association.

[64]  J. Ellner,et al.  Stress as a precipitating factor in subjects with recurrent herpes labialis. , 1985, The Journal of family practice.

[65]  M. Demitrack,et al.  Chronic Fatigue Syndrome: An Integrative Approach to Evaluation and Treatment , 1999 .

[66]  O. J. Trask,et al.  Spousal caregivers of dementia victims: longitudinal changes in immunity and health. , 1991, Psychosomatic medicine.

[67]  B. Gebhardt,et al.  Mechanisms of herpes simplex virus type 1 reactivation , 1996, Journal of virology.

[68]  W. Henle,et al.  Antibodies to Epstein-Barr virus-related antigens in nasopharyngeal carcinoma. Comparison of active cases with long-term survivors. , 1973, Journal of the National Cancer Institute.

[69]  J. Sheridan,et al.  Restraint stress differentially affects anti-viral cellular and humoral immune responses in mice , 1991, Journal of Neuroimmunology.

[70]  J. Sheridan,et al.  Stress-induced effects on cell-mediated innate and adaptive memory components of the murine immune response to herpes simplex virus infection , 1991, Brain, Behavior, and Immunity.

[71]  R. Schooley,et al.  Antibodies to Epstein-Barr virus-specific DNase and DNA polymerase in the chronic fatigue syndrome. , 1988, Archives of internal medicine.

[72]  G. Bauer Induction of epstein‐barr virus early antigens by corticosteroids: Inhibition by TPA and retinoic acid , 1983, International journal of cancer.

[73]  D. Bell,et al.  Interleukin-2 and the chronic fatigue syndrome. , 1989, Annals of Internal Medicine.

[74]  I. Hickie,et al.  Cell‐mediated immunity in patients with chronic fatigue syndrome, healthy control subjects and patients with major depression , 1992, Clinical and experimental immunology.

[75]  K. Yamanishi,et al.  Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome. , 1995, Intervirology.

[76]  E. M. Smith,et al.  Human lymphocyte production of corticotropin and endorphin-like substances: association with leukocyte interferon. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[77]  J. Sheridan,et al.  Stress-induced modulation of the primary cellular immune response to herpes simplex virus infection is mediated by both adrenal-dependent and independent mechanisms , 1993, Journal of Neuroimmunology.

[78]  J. Kiecolt-Glaser,et al.  “Relatively mild stress” depresses cellular immunity in healthy adults , 1985, Behavioral and Brain Sciences.