NICOTINAMIDE DECREASES CYTOKINE-INDUCED ACTIVATION OF ORBITAL FIBROBLASTS FROM PATIENTS WITH THYROID-ASSOCIATED OPHTHALMOPATHY

We used now cytometry to investigate the effects of nicotinamide, an i nhibitor of poly (ADP ribose) synthetase, on the cell-surface expressi on of cytokine-induced human leukocyte antigen (HLA)-A,B,C antigen, HL A-DR antigen, intercellular adhesion molecule 1, CD44, and Fas express ion in cultured orbital fibroblasts from patients with thyroid-associa ted ophthalmopathy. After two to seven passages, cultured orbital fibr oblasts were incubated for 3 days with interferon gamma or tumor necro sis factor alpha in the presence of nicotinamide. Nicotinamide inhibit ed the induction of both HLA-DR and intercellular adhesion molecule 1 expression by cytokines on fibroblasts but did not interfere with indu ction of HLA-A,B,C, or CD44 expression. Nicotinamide also inhibited th e proliferation of orbital fibroblasts, as assessed by a [H-3]-thymidi ne incorporation assay and cell counts. Nicotinamide also enhanced the expression of the apoptosis-mediating protein Fas on fibroblasts. Our data suggest that nicotinamide inhibits cytokine-induced activation o f fibroblasts and thus may decrease the autoimmune injury to the orbit in thyroid-associated ophthalmopathy.