Glucocorticoid receptors are down-regulated in inflamed colonic mucosa butnot in peripheral blood mononuclear cells from patients with inflammatory bowel disease

Background Growing evidence indicates that the immune system and the hypoth alamic-pituitary-adrenal system are linked by several mechanisms, for examp le intracellular glucocorticoid receptors (hGR). Glucocorticoids are the st andard treatment of acute attacks of inflammatory bowel disease (IBD). Bind ing of glucocorticoids to hGR down-regulates the transcription of inflammat ory genes that can propagate IBD. Patients and methods IBD patients were either treated with 5-60 mg of predn isolone for more than 1 week or were without glucocorticoid treatment for m ore than 4 weeks, hGR levels were determined from isolated cytosol of perip heral blood mononuclear cells (PBMCs) or mucosal biopsies using a radioassa y with [H-3]-dexamethasone. Interleukin (IL) 6 levels were determined by en zyme-linked immunosorbent assay (ELISA). Results The systemic (PBMC) hGR levels of corticosteroid-treated IBD patien ts were significantly lower than those of control subjects (59.6 +/- 57.1 d pm mg(-1) cytosol protein vs. 227.0 +/- 90.8 dpm mg(-1) cytosol protein, P = 0.007) and IBD patients not receiving glucocorticoid treatment (179.7 +/- 171.3 dpm mg(-1) cytosol protein, P = 0.002). Systemic hGR levels in untre ated IBD patients did not differ significantly from those in control subjec ts. In patients with connective tissue diseases, systemic hGR levels were a lso found to be decreased in the absence of glucocorticoid treatment. Syste mic hGR levels in patients with Crohn's disease (CD) treated with steroids (66.6 +/- 61.0 dpm mg(-1) cytosol protein) were not different from those in patients with ulcerative colitis (UC) (56.1 +/- 51.6 dpm mg(-1) cytosol pr otein). In contrast to these findings, mucosal hGR levels were significantl y decreased in both steroid-treated (18.0 +/- 15.5) and not steroid-treated (37.8 +/- 30.5) patients compared with control subjects (125.6 +/- 97.1; P = 0.00009 and P = 0.0008 respectively). IL-6 levels in all IBD groups with and without steroids were significantly different from those in control su bjects. Conclusion In IBD there is no difference in systemic hGR levels between not steroid-treated patients and control subjects, in spite of inflammatory ac tivity (IL-6). Mucosal hGR levels were decreased independently of treatment , probably leading to a decreased protection against NF-kappa B action in t he intestinal mucosa.