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 sensi tivity 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 glucocortic oids in vitro, Results: Affinity (Kd) and number of GR was not different in PBMC of CFS pa tients 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+/-1616/cell), Moreover, RT-PC R revealed no differences in GR messenger RNA expression, Nevertheless, PBM C from CFS patients showed an increased sensitivity to glucocorticoids in v itro. In CFS patients 0.01 mu mol dexamethasone suppressed PBMC proliferati on by 37%, whereas the controls were only suppressed by 17% (P<0.01). Addit ion of phorbol 12-myristate 13-acetate to the cultures rendered the cells r esistant to dexamethasone with regard to proliferation and IL-10 and IFN-<g amma> production, but not to IL-2 and TNF-alpha production in both patients and controls, No difference between patients and controls,vas observed in this respect. Conclusions: In conclusion, PBMC of CFS patients display an increased sensi tivity 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.