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

Abstract

OBJECTIVE: Glucocorticoids are widely used in the treatment of inflammatory bowel disease (IBD). Up- and down-regulated expression of glucocorticoid receptors (GR) has been reported for different chronic inflammatory diseases. The aim of this study was to investigate the expression of GR and their apparent dissociation constant (K(d)) in patients with IBD. METHODS: Thirty-nine patients with IBD (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. Peripheral blood mononuclear cells from patients and controls were isolated using the Ficoll-Hypaque gradient and a whole cell [3H]-dexamethasone binding assay and Scatchard plot analysis were performed to assess GR number and the apparent 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 per 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). Expression of GR in IBD patients was suppressed to normal levels under steroid treatment (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 and the control group. CONCLUSIONS: Our data show a systemic increase in GR expression and a decrease in the affinity to the GR in IBD, in contrast to other inflammatory diseases such as rheumatoid arthritis and asthma. These changes point towards a systemic character of IBD, which might be considered in a decision between topical and systemic treatment. (C) 2000 by Am. Coll. of Gastroenterology.