Interleukin-1 Receptor Antagonist Ribonucleic Acid and Protein Expression by Cultured Graves’ and Normal Orbital Fibroblasts Is Differentially Modulated by Dexamethasone and Irradiation

Recent data have indicated that orbital fibroblasts (OF) can be stimulated to produce marked quantities of interleukin-1 receptor antagonist (IL-1RA), a powerful inhibitor of the proinflammatory activities of interleukin-1 in the orbital tissues in Graves’ ophthalmopathy (GO). We examined whether the beneficial effects of dexamethasone or irradiation, the two main therapeutic modalities applied in patients with active GO, may be related to their capacity to alter IL-1RA ribonucleic acid (RNA) and protein expression in OF. Early passages of cultured OF were obtained from orbital connective tissue and extraocular muscle of patients with severe active GO and five control subjects. Modulation of the two variants of IL-1RA, intracellular IL-1RA (icIL-1RA) and soluble IL-1RA (sIL-1RA), was studied after exposure of OF to increasing concentrations of dexamethasone (10−10-10−6 mol/L), the glucocorticoid receptor antagonist RU 38486 (10−3 mol/L), or combinations thereof. Alternatively, cell monolayers were exposed...