Title
Increased sensitivity to glucocorticoids in peripheral blood mononuclear cells of chronic fatigue syndrome patients, without evidence for altered density or affinity of glucocorticoid receptors
Author
Visser, J.
Lentjes, E.
Haspels, I.
Graffelman, W.
Blauw, B.
de Kloet, R.
Nagelkerken, L.
TNO Preventie en Gezondheid
Publication year
2001
Abstract
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
Subject
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
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TNO identifier
236002
ISSN
1081-5589
Source
Journal of Investigative Medicine, 49 (2), 195-204
Document type
article