Changes in Immune Parameters Seen in Gulf War Veterans but Not in Civilians with Chronic Fatigue Syndrome

ABSTRACT The purpose of this study was to evaluate immune function through the assessment of lymphocyte subpopulations (total T cells, major histocompatibility complex [MHC] I- and II-restricted T cells, B cells, NK cells, MHC II-restricted T-cell-derived naive and memory cells, and several MHC I-restricted T-cell activation markers) and the measurement of cytokine gene expression (interleukin 2 [IL-2], IL-4, IL-6, IL-10, IL-12, gamma interferon [IFN-γ], and tumor necrosis factor alpha [TNF-α]) from peripheral blood lymphocytes. Subjects included two groups of patients meeting published case definitions for chronic fatigue syndrome (CFS)—a group of veterans who developed their illness following their return home from participating in the Gulf War and a group of nonveterans who developed the illness sporadically. Case control comparison groups were comprised of healthy Gulf War veterans and nonveterans, respectively. We found no significant difference for any of the immune variables in the nonveteran population. In contrast, veterans with CFS had significantly more total T cells and MHC II+ T cells and a significantly higher percentage of these lymphocyte subpopulations, as well as a significantly lower percentage of NK cells, than the respective controls. In addition, veterans with CFS had significantly higher levels of IL-2, IL-10, IFN-γ, and TNF-α than the controls. These data do not support the hypothesis of immune dysfunction in the genesis of CFS for sporadic cases of CFS but do suggest that service in the Persian Gulf is associated with an altered immune status in veterans who returned with severe fatiguing illness.

[1]  N. Laird,et al.  Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data. , 1997, Statistics in medicine.

[2]  A. O’Garra,et al.  Cytokines induce the development of functionally heterogeneous T helper cell subsets. , 1998, Immunity.

[3]  Hocke,et al.  INDUCTION OF DIFFERENTIATION BY IL-6-TYPE CYTOKINES IS IMPAIRED IN MYELOID LEUKAEMIA CELLS UNABLE TO ACTIVATE Stat5a. , 1997, Cytokine.

[4]  J. Ceuppens,et al.  Interleukin 12 and B7/CD28 interaction synergistically upregulate interleukin 10 production by human T cells. , 1997, Cytokine.

[5]  H. Kanegane,et al.  Viral interleukin-10 in chronic active Epstein-Barr virus infection. , 1997, The Journal of infectious diseases.

[6]  Alimuddin Zumla,et al.  Gulf War syndrome: is it due to a systemic shift in cytokine balance towards a Th2 profile? , 1997, The Lancet.

[7]  Susan K. Johnson,et al.  Cognitive functioning is impaired in patients with chronic fatigue syndrome devoid of psychiatric disease. , 1997, Journal of neurology, neurosurgery, and psychiatry.

[8]  D. Buchwald,et al.  Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome. , 1997, The Journal of rheumatology.

[9]  T. Shirakawa,et al.  The Inverse Association Between Tuberculin Responses and Atopic Disorder , 1996, Science.

[10]  R. Littell SAS System for Mixed Models , 1996 .

[11]  M. Irwin,et al.  Partial night sleep deprivation reduces natural killer and celhdar immune responses in humans , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[12]  G. Bleijenberg,et al.  Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome. , 1996, The Journal of infectious diseases.

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

[14]  W. Gause,et al.  The use of the PCR to quantitate gene expression. , 1994, PCR methods and applications.

[15]  F. Finkelman,et al.  Effects of IL-12 on in vivo cytokine gene expression and Ig isotype selection. , 1994, Journal of immunology.

[16]  C. Dinarello,et al.  Measuring circulating cytokines. , 1993, Journal of applied physiology.

[17]  F. Finkelman,et al.  A primary intestinal helminthic infection rapidly induces a gut-associated elevation of Th2-associated cytokines and IL-3. , 1993, Journal of immunology.

[18]  Richard H. Jones Analysis of repeated measures , 1992 .

[19]  P. Forsberg,et al.  Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome. , 1992, The Journal of infectious diseases.

[20]  R. Yogev,et al.  Lymphocyte subsets in healthy children during the first 5 years of life. , 1992, JAMA.

[21]  F. Finkelman,et al.  Cytokine gene expression after in vivo primary immunization with goat antibody to mouse IgD antibody. , 1991, Journal of immunology.

[22]  J. Levy,et al.  Chronic fatigue syndrome: clinical condition associated with immune activation , 1991, The Lancet.

[23]  M. Tsang,et al.  Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome. , 1991, Cytokine.

[24]  B. Pedersen Influence of Physical Activity on the Cellular Immune System: Mechanisms of Action , 1991, International journal of sports medicine.

[25]  S. Gupta,et al.  A Comprehensive Immunological Analysis in Chronic Fatigue Syndrome , 1991, Scandinavian journal of immunology.

[26]  I. Hickie,et al.  Immunological abnormalities in the chronic fatigue syndrome , 1990, The Medical journal of Australia.

[27]  F. Sánchez‐Franco,et al.  Thyroid Hormone Action on ACTH Secretion , 1989, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[28]  D. Wakefield,et al.  Immunological abnormalities in the chronic fatigue syndrome (for editorial comment, see page 117) , 1989 .

[29]  A. Komaroff Chronic fatigue syndromes: relationship to chronic viral infections. , 1988, Journal of virological methods.

[30]  James F. Jones,et al.  Chronic fatigue syndrome: a working case definition. , 1988, Annals of internal medicine.

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

[32]  D. R. Thomas,et al.  Univariate repeated measures techniques applied to multivariate data , 1983 .

[33]  J. Ware,et al.  Random-effects models for longitudinal data. , 1982, Biometrics.

[34]  J. DeLuca,et al.  Medical evaluation of Persian Gulf veterans with fatigue and/or chemical sensitivity. , 1998, Journal of medicine.

[35]  A. Starr,et al.  Cytokine production by adherent and non-adherent mononuclear cells in chronic fatigue syndrome. , 1997, Journal of psychiatric research.

[36]  S. Wessely,et al.  Clinical improvement in chronic fatigue syndrome is not associated with lymphocyte subsets of function or activation. , 1997, Clinical immunology and immunopathology.

[37]  W. Reeves,et al.  Immune responses associated with chronic fatigue syndrome: a case-control study. , 1997, The Journal of infectious diseases.

[38]  N. H. Timm,et al.  Univariate and Multivariate General Linear Models: Theory and Applications Using SAS â Software , 1997 .

[39]  M. Antoni,et al.  Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression. , 1994, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.