Bucillamine의 항류마티스 작용중 임파구에 대한 효과

Abstract

Objective: Bucillamine[N-(2-mercapto-2-methylpropionyl)-L-cysteine] (BUC) is a thiol compound that differs from D-pencillamine(DPC) in that it contains two free sulfhydryl groups. Clinical trials have suggested that the efficacy of BUC in rheumatoid arthritis (RA) is as effective as DPC, but the mechanism of action remains unclear. We therefore examined the effects of BUC on the in vitro function of human B cell and T cell in comparision to those of DPC. Methods: The effect of BUC and DPC on Staphylococcus aureus Cowan l (SAC) induced IgM production by B cells from 11 healthy donors was examined. Phytohemagglutinin (PHA) induced proliferation and Interferon-r(IFN-r) and Interleukin-2 (IL-2) production by T cells was also examined. Results: BUC and BUC-ID(SA981) suppressed the production of IgM at concentration of 0.1-100 ug/ml, whereas DPC suppressed at concentration of 100 ug/ml. BUC and DPC inhibited PHA induced DNA synthesis of peripheral blood mononuclear cells (PBMCs) and T cell in a dose-dependent manner. DPC (10 ug/ml) significantly suppresed IFN-r production by PHA-stimulated T cells, but not suppressed IL-2 production, whereas BUC(10 ug/ml) not significantly suppressed IFN -r and IL-2 production. Conclusion: BUC has immunosuppressive effects inhibiting the function of B cells and T cell proliferation, whereas the action of DPC is targeted at T lymphocytes. BUC may be effective in rheumatoid factor positive RA patients who have not responded to treatment with DPC.