抄録
Effects of anti-rheumatic drugs, gold sodium thiomalate (GST), methotrexate (MTX), D-penicillamine (D-P) and bucillamine (BU), on rhIL-1β-induced nitric oxide (NO) production in rat synovial fibroblast-like cells (SFC) cultured in vitro were investigated. The SFC (passage 4) were cultured for 48hrs in Dulbecco's modified Eagle's medium containing an NO inducer, LPS or rhIL-1β. NO production by SFC was assessed by using Griess reagent. RhIL-1β but not LPS, induced a significant increase in NO production in SFC. The rhIL-1β-induced NO production was inhibited by the presence of GST in a dose dependent manner, whereas MTX (100 ng/ml) had no effect. In contrast, both D-P (10 μg/ml) and BU (3 μg/ml) significantly stimulated rhIL-1β-induced NO production in SFC. This effect of SH-containing antirheumatic drugs was completely abolished by the presence of NO inhibitors, aminoguanidine (AG : 1 mM) and cycloheximide (CH : 2 μM) . AG but not CH, added at a later stage of culture (24-48hrs) abolished rhiL 1β induced NO production, indicating that these SH-compounds stimulate NO synthase activity in SFC.
The present study suggests that SH-anti-rheumatic drugs stimulate rhIL-1β-induced NO production in SFC, and that the increase in NO may partly inhibit the bone destruction in rheumatoid arthritis.
