REGULATION BY GLUCOCORTICOIDS OF INTERFERON-GAMMA-INDUCED HLA-DR ANTIGEN EXPRESSION IN CULTURED HUMAN ORBITAL FIBROBLASTS

OBJECTIVE The purpose of this study was to determine whether glucocorticoids can block the induction of HLA-DR antigen expression by interferon gamma in human fibroblasts in culture. DESIGN AND PATIENTS Confluent cultures of fibroblasts derived from the orbit or the skin of patients with Graves' ophthalmopathy or from normal subjects were treated with interferon gamma (100 U/ml) without or with graded concentrations of steroids. MEASUREMENTS Cultures were analysed for HLA-DR expression using quantitative immunoblotting and indirect immunofluorescence. RESULTS Glucocorticoids could block HLA-DR induction in a dose-dependent manner. At 10(-6) mol/l, the steroids dexamethasone and RU 28362 inhibited expression by 70% (P < 0.004) and 56% (P < 0.002) respectively. RU 38486, a glucocorticoid antagonist, could reverse the effect of both glucocorticoids, an action that was also dose dependent. At 10(-5) mol/l, RU 38486 blocked virtually the entire glucocorticoid effect. CONCLUSIONS These results suggest that glucocorticoids can regulate HLA-DR induction by interferon gamma at physiological concentrations, an action which is stereo-specific and mediated through the glucocorticoid receptor.