Higher expression of glucocorticoid receptor in peripheral mononuclear cells in inflammatory bowel disease

OBJECTIVE: Glucocorticoids are widely used in the treatment of inflammatory bowel disease (IBD). Up- and down-regulated expression of glucocorticoid r eceptors (GR) has been reported for different chronic inflammatory diseases . The aim of this study was to investigate the expression of GR and their a pparent dissociation constant (K-d) in patients with IBD. METHODS: Thirty-nine patients with LED (22 with ulcerative colitis, 17 with Crohn's disease) and 35 normal controls were studied. Twenty-five patients did not receive steroids, 14 patients were treated with steroids. Peripher al blood mononuclear cells from patients and controls were isolated using t he Ficoll-Hypaque gradient and a whole cell [H-3]-dexamethasone binding ass ay and Scatchard plot analysis were performed to assess GR number and the a pparent dissociation constant. Results were expressed as mean +/- standard deviation. RESULTS: Normal controls showed an expression of 3969 +/- 1555 GR per cell with an apparent dissociation constant of 6.16 +/- 3.8 nmol/L. IBD patients without steroids had a significant increase both in the expression of GR p er cell (6401 +/- 2344; p < 0.0001; Wilcoxon-Mann-Whitney test) and in the apparent dissociation constant (11.02 +/- 7.57 nmol/L; p = 0.006). Expressi on of GR in LED patients was suppressed to normal levels under steroid trea tment (4594 +/- 2237; p = 0.024), but K-d remained elevated (13.56 +/- 9.05 nmol/L). Plasma cortisol levels were not different between IBD patients an d the control group. CONCLUSIONS: Our data show a systemic increase in GR expression and a decre ase in the affinity to the GR in IBD, in contrast to other inflammatory dis eases such as rheumatoid arthritis and asthma. These changes point towards a systemic character of IBD, which might be considered in a decision betwee n topical and systemic treatment. (C) 2000 by Am. Cell. of Gastroenterology .