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Enhanced glucocorticoid sensitivity in patients with chronic fatigue syndrome

Published online by Cambridge University Press:  24 June 2014

Jens Gaab ,
Nicolas Rohleder ,
Vera Heitz ,
Tanja Schad ,
Veronika Engert ,
Thomas H Schürmeyer  and
Ulrike Ehlert
Jens Gaab*
Affiliation:
Center for Psychobiological and Psychosomatic Research, University of Trier, Germany
Nicolas Rohleder
Affiliation:
Center for Psychobiological and Psychosomatic Research, University of Trier, Germany
Vera Heitz
Affiliation:
Center for Psychobiological and Psychosomatic Research, University of Trier, Germany
Tanja Schad
Affiliation:
Center for Psychobiological and Psychosomatic Research, University of Trier, Germany
Veronika Engert
Affiliation:
Center for Psychobiological and Psychosomatic Research, University of Trier, Germany
Thomas H Schürmeyer
Affiliation:
Center for Psychobiological and Psychosomatic Research, University of Trier, Germany
Ulrike Ehlert
Affiliation:
Center for Psychobiological and Psychosomatic Research, University of Trier, Germany
*
Dr phil. Jens Gaab, Institute for Psychology, Clinical Psychology II, University of Zürich, Zürichbergstr. 43, CH-8044 Zürich, Switzerland. Tel. + 41 16343096; Fax: + 41 16343696. E-mail: jgaab@klipsy.unizh.ch
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Abstract

Objective:

Alterations of the immune–neuroendocrine interplay have been described in chronic fatigue syndrome (CFS). Employing a recently developed method, the study set out to investigate whether patients with CFS have an altered sensitivity to glucocorticoids (GCs) when under stress.

Methods:

A total of 21 CFS patients and 20 healthy age- and gender-matched controls underwent a standardized psychosocial stress test (Trier Social Stress Test, TSST). Salivary and plasma cortisol levels were measured repeatedly following exposure to the stressor. GC sensitivity was assessed in vitro by dexamethasone inhibition of lipopolysaccharide-stimulated production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNC-α).

Results:

Cortisol responses following the TSST did not differ significantly between CFS patients and healthy controls. GC sensitivity differed significantly between CFS patients and healthy controls, with CFS patients showing a greater sensitivity towards GCs (TNF-α: F1/39 = 7.32, P = 0.01; IL-6: F1/39 = 9.73, P = 0.004).

Conclusion:

Consistent with recent evidence, CFS patients are characterized by an enhanced sensitivity to glucocorticoids. The implications for secondary processes, such as the regulatory influence of glucocorticoids on immune processes, are discussed.

Keywords

ACTHchronic fatigue syndromecortisoldexamethasoneglucocorticoid sensitivityHPA axisinterleukin-6psychosocial stresstumor necrosis factor-alpha

Information

Type
Research Article
Information
Acta Neuropsychiatrica , Volume 15 , Issue 4 , August 2003 , pp. 184 - 191
Copyright
Copyright © 2003 Blackwell Munksgaard

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References

Fukuda, K, Straus, SE, Hickie, I, Sharpe, MC, Dobbins, JG, Komaroff, A. The chronic fatigue syndrome. a comprehensive approach to its definition and study. Int Chronic Fatigue Syndrome Study Group Ann Intern Med 1994;121: 953–959. Google ScholarPubMed
Demitrack, MA. The psychobiology of chronic fatigue syndrome: the central nervous system as a common pathway. In: Demitrack, MA, Abbey, SE, eds. Chronic Fatigue Syndrome: an Integrative Approach to Evaluation and Treatment. New York: The Guildford Press, 1997: 72–112. Google Scholar
Ehlert, U, Gaab, J, Heinrichs, M. Psychoneuroendocrinological contributions to the etiology of depression, posttraumatic stress disorder, and stress-related bodily disorders: the role of the hypothalamus-pituitary-adrenal axis. Biol Psychol 2001;57: 141–152.CrossRefGoogle ScholarPubMed
Theorell, T, Blomkvist, V, Lindh, G, Evengard, B. Critical life events, infections, and symptoms during the year preceding chronic fatigue syndrome (CFS): an examination of CFS patients and subjects with a nonspecific life crisis. Psychosom Med 1999; 61: 304–310.CrossRefGoogle ScholarPubMed
Lutgendorf, SK, Antoni, Mh, Ironson, Get al. Physical symptoms of chronic fatigue syndrome are exacerbated by the stress of Hurricane Andrew. Psychosom Med 1995;57: 310–323.CrossRefGoogle ScholarPubMed
Gaab, J, Hüster, D, Peisen, Ret al. Hypothamalus-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological and pharmacological stimulation. Psychosom Med 2002;64(6): 951–962. Google Scholar
Gaab, J, Engert, V, Heitz, V, Schad, T, Schürmeyer, T, Ehlert, U. Associations between neuroendocrine responses to insulin tolerance test and patient characteristics in chronic fatigue syndrome. J Psychosom Res, Special issue on somatoform disorders.Google Scholar
Clauw, DJ, Chrousos, GP. Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation 1997;4: 134–153.CrossRefGoogle ScholarPubMed
Parker, AJ, Wessely, S, Cleare, AJ. The neuroendocrinology of chronic fatigue syndrome and fibromyalgia. Psychol Med 2001;31: 1331–1345.CrossRefGoogle ScholarPubMed
Ur, E, White, PD, Grossman, A. Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome. Eur Arch Psychiatr Clin Neurosci 1992;241: 317–322. CrossRefGoogle ScholarPubMed
Vollmer-Conna, U, Lloyd, A, Hickie, I, Wakefield, D. Chronic fatigue syndrome: an immunological perspective. Aust NZ J Psychiatry 1998;32: 523–527. CrossRefGoogle ScholarPubMed
Patarca, R. Cytokines and chronic fatigue syndrome. Ann N Y Acad Sci 2001;933: 185–200.CrossRefGoogle ScholarPubMed
Visser, JT, De Kloet, ER, Nagelkerken, L. Altered glucocorticoid regulation of the immune response in the chronic fatigue syndrome. Ann NY Acad Sci 2000;917: 868–875.CrossRefGoogle ScholarPubMed
Sternberg, EM. Neuroendocrine regulation of autoimmune/inflammatory disease. J Endocrinol 2001; 169: 429–435.CrossRefGoogle ScholarPubMed
McKay, LI, Cidlowski, JA. Molecular control of immune/inflammatory responses: interactions between nuclear factor-kappa B and steroid receptor-signaling pathways. Endocr Rev 1999;20: 435–459.Google ScholarPubMed
Rohleder, N, Schommer, NC, Hellhammer, Dh, Engel, R, Kirschbaum, C. Sex differences in glucocorticoid sensitivity of proinflammatory cytokine production after psychosocial stress. Psychosom Med 2001;63: 966–972.CrossRefGoogle ScholarPubMed
Derijk, R, Michelson, D, Karp, Bet al. Exercise and circadian rhythm-induced variations in plasma cortisol differentially regulate interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) production in humans: high sensitivity of TNF alpha and resistance of IL-6. J Clin Endocrinol Metabol 1997; 82: 2182–2191. Google ScholarPubMed
Visser, J, Blauw, B, Hinloopen, Bet al. CD4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-gamma production and increased sensitivity to dexamethasone. J Infect Disord 1998; 177: 451–454. CrossRefGoogle ScholarPubMed
Visser, J, Graffelman, W, Blauw, Bet al. LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome patients is increased but supersensitive to inhibition by dexamethasone. J Neuroimmunol 2001;119: 343–349.CrossRefGoogle ScholarPubMed
Visser, J, Lentjes, E, Haspels, Iet al. Increased sensitivity to glucocorticoids in peripheral blood mononuclear cells of chronic fatigue syndrome patients, without evidence for altered density or affinity of glucocorticoid receptors. J Invest Med 2001;49: 195–204. CrossRefGoogle ScholarPubMed
Gaab, J, Engert, V, Schad, T, Schürmeyer, T, Hellhammer, D, Ehlert, U. Enhanced suppression of salivary free cortisol following the low dose dexamethasone suppression test in chronic fatigue syndrome. Psychosom Med 2001;663: 95. Google Scholar
Demitrack, MA, Dale, JK, Straus, SEet al. Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metabol 1991;73: 1224–1234. CrossRefGoogle ScholarPubMed
Gaab, J, Hüster, D, Peisen, Ret al. Combined low and high dose synacthen test in patients with chronic fatigue syndrome and healthy controls. Psychosomatics 2003; 44: 113–119. Google Scholar
Wittchen, HU, Lachner, G, Wunderlich, U, Pfister, H. Test-retest reliability of the computerized DSM-IV version of the Munich-Composite International Diagnostic Interview (M-CIDI). Soc Psychiatry Psychiatr Epidemiol 1998;33: 568–578.CrossRefGoogle Scholar
Kirschbaum, C, Pirke, KM, Hellhammer, Dh. The ‘Trier Social Stress Test’– a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 1993;28: 76–81.CrossRefGoogle Scholar
Dressendorfer, RA, Kirschbaum, C, Rohde, W, Stahl, F, Strasburger, CJ. Synthesis of a cortisol-biotin conjugate and evaluation as a tracer in an immunoassay for salivary cortisol measurement. J Steroid Biochem Mol Biol 1992;43: 683–692.CrossRefGoogle Scholar
Chalder, T, Berelowitz, G, Pawlikowska, Tet al. Development of a fatigue scale. J Psychosom Res 1993;37: 147–153.CrossRefGoogle ScholarPubMed
Kessler, S, Jaeckel, W, Cziske, R. Assessing health in musculoskeletal disorders – the appropriateness of a German version of the Sickness Impact Profile. Rheumatol Int 1997;17: 119–125.CrossRefGoogle ScholarPubMed
Herrmann, C, Buss, U, Snaith, RP. HADS-D Hospital Anxiety and Depression Scale – Ein Fragebogen zur Erfassung von Angst und Depressivität in der somatischen Medizin. Göttingen: Hans Huber, 1995. Google Scholar
Franke, G. Die Symptom-Checkliste von Derogatis – Deutsche Version. Göttingen: Beltz Test GmbH, 1995. Google Scholar
Cannon, JG, Angel, JB, Abad, LW et al. Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatique syndrome. J Clin Immunol 1998;18(4): 291–298.CrossRefGoogle Scholar
Kavelaars, A, Kuis, W, Knook, L, Sinnema, G, Heijnen, CJ. Disturbed neuroendocrine–immune interactions in chronic fatigue syndrome. J Clin Endocrinol Metabol 2000;85: 692–696. Google ScholarPubMed
Visser, J, Van Boxel-Dezaire, A, Methorst, D, Brunt, T, De Kloet, ER, Nagelkerken, L. Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in vitro. Blood 1998;91: 4255–4264.Google ScholarPubMed
Peterson, PK, Sirr, SA, Grammith, FCet al. Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients. Clin Diagn Laboratory Immunol 1994;1: 222–226. Google ScholarPubMed
Lloyd, A, Gandevia, S, Brockman, A, Hales, J, Wakefield, D. Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise. Clin Infect Disord 1994;18: S142–S146. CrossRefGoogle Scholar
Lamanca, JJ, Sisto, SA, Zhou, XDet al. Immunological response in chronic fatigue syndrome following a graded exercise test to exhaustion. J Clin Immunol 1999;19: 135–142.CrossRefGoogle ScholarPubMed
Papanicolaou, DA, Tsigos, C, Oldfield, Eh, Chrousos, GP. Acute glucocorticoid deficiency is associated with plasma elevations of interleukin-6: does the latter participate in the symptomatology of the steroid withdrawal syndrome and adrenal insufficiency? J Clin Endocrinol Metabol 1996;81: 2303–2306. CrossRefGoogle ScholarPubMed
Glaser, R, Kiecolt-Glaser, JK. Stress-associated immune modulation: relevance to viral infections and chronic fatigue syndrome. Am J Med 1998;105: 35–42S. CrossRefGoogle ScholarPubMed
Heim, C, Ehlert, U, Hellhammer, DH. The potential role of hypocortisolism in the pathophysiology of stress- related bodily disorders. Psychoneuroendocrinology 2000;25: 1–35.CrossRefGoogle ScholarPubMed
Bodner, G, Ho, A, Kreek, MJ. Effect of endogenous cortisol levels on natural killer cell activity in healthy humans. Brain Behav Immun 1998;12: 285–296.CrossRefGoogle ScholarPubMed
Agarwal, SK, Marshall, GD Jr.Glucocorticoid-induced type 1/type 2 cytokine alterations in humans: a model for stress-related immune dysfunction. J Interferon Cytokine Res 1998;18: 1059–1068.CrossRefGoogle ScholarPubMed
Gaab, J, Huster, D, Peisen, Ret al. Low-dose dexamethasone suppression test in chronic fatigue syndrome and health. Psychosom Med 2002;64: 311–318.CrossRefGoogle ScholarPubMed
Rief, W, Pilger, F, Ihle, D, Bosmans, E, Egyed, B, Maes, M. Immunological differences between patients with major depression and somatization syndrome. Psychiatry Res 2002;105: 165–174. CrossRefGoogle ScholarPubMed