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Increased sensitivity to glucocorticoids in peripheral blood mononuclear cells of chronic fatigue syndrome patients, without evidence for altered density or affinity of glucocorticoid receptors

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Author: Visser, J. · Lentjes, E. · Haspels, I. · Graffelman, W. · Blauw, B. · Kloet, R. de · Nagelkerken, L.
Institution: TNO Preventie en Gezondheid
Source:Journal of Investigative Medicine, 2, 49, 195-204
Identifier: 236002
Keywords: Health · Chronic fatigue syndrome · Glucocorticoid receptors · Glucocorticoids · Dexamethasone · Gamma interferon · Glucocorticoid · Glucocorticoid receptor · Interleukin 10 · Interleukin 2 · Iessenger RNA · Phorbol 13 acetate 12 myristate · Tumor necrosis factor alpha · Clinical article · controlled study · Corticotropin blood level · Cytokine production · Enzyme linked immunosorbent assay · Hormone sensitivity · Human cell · Hydrocortisone blood level · Mononuclear cell · receptor affinity · receptor density · reverse transcription polymerase chain reaction · Adolescent · Adrenocorticotropic Hormone · Adult · Cells, Cultured · Cytokines · Dexamethasone · Fatigue Syndrome, Chronic · Female · Humans · Hydrocortisone · Leukocytes, Mononuclear · Male · Middle Aged · Receptors, Glucocorticoid · Tetradecanoylphorbol Acetate


Background: In this study we tested the hypothesis that the increased sensitivity to glucocorticoids in chronic fatigue syndrome (CFS)-patients can be attributed to an altered functioning of their glucocorticoid receptors (GR). Methods: For this purpose, affinity and distribution of the GR were studied in purified, peripheral blood mononuclear cells (PBMC) of 10 CFS patients and 14 controls along with the responsiveness of these cells to glucocorticoids in vitro. Results: Affinity (Kd) and number of GR was not different in PBMC of CFS patients when compared with the controls (Kd, 12.9±8.9 nmol vs 18.8±16.2 nmol and GR number, 4839±2824/ cell vs 4906±1646/cell). Moreover, RT-PCR revealed no differences in GR messenger RNA expression. Nevertheless, PBMC from CFS patients showed an increased sensitivity to glucocorticoids in vitro. In CFS patients 0.01 μmol dexamethasone suppressed PBMC proliferation by 37%, whereas the controls were only suppressed by 17% (P<0.01). Addition of phorbol 12-myristate 13-acetate to the cultures rendered the cells resistant to dexamethasone with regard to proliferation and IL-10 and IFN-γ production, but not to IL-2 and TNF-α production in both patients and controls. No difference between patients and controls was observed in this respect. Conclusions: In conclusion, PBMC of CFS patients display an increased sensitivity to glucocorticoids, which cannot be explained by number or affinity of the GR but should rather be attributed to molecular processes beyond the actual binding of the ligand to the GR. Chemicals/CAS: Adrenocorticotropic Hormone, 9002-60-2; Cytokines; Dexamethasone, 50-02-2; Hydrocortisone, 50-23-7; Receptors, Glucocorticoid; Tetradecanoylphorbol Acetate, 16561-29-8