Increased sensitivity to glucocorticoids in peripheral blood mononuclear cells of chronic fatigue syndrome patients, without evidence for altered density or affinity of glucocorticoid receptors.
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, 4,839 +/- 2,824/ cell vs 4,906 +/- 1,646/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 micromol 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-gamma production, but not to IL-2 and TNF-alpha 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.
Visser
J
J
Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands.
Lentjes
E
E
Haspels
I
I
Graffelman
W
W
Blauw
B
B
de Kloet
R
R
Nagelkerken
L
L
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D015673:Fatigue Syndrome, Chronic / Q000097:blood*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000032:analysis* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016207:Cytokines; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone