SYNERGISTIC INHIBITION OF T-CELL PROLIFERATION BY GOLD SODIUM THIOMALATE AND AURANOFIN

Objectve. Gold compounds have been employed as therapeutic agents for rheumatoid arthritis (RA) for many years, but the molecular mechanism of their action is unknown. Our studies were undertaken to compare the immunosuppressive activities of parenteral gold (gold sodium thiomala te; GSTM) and orally active gold (auranofin; AF). Methods. The effects of GSTM and AF on in vitro models of human T cell activation were exa mined. Results. GSTM and AF were found to exert a synergistic inhibito ry effect on human T lymphocyte proliferation in vitro. The concentrat ions of GSTM and AF that synergistically inhibit T cell proliferation were easily attainable in the serum or synovium of patients treated wi th these agents. The synergistic inhibitory effect of GSTM and AF was not apparent when interleukin 2 (IL-2)R expression or IL-2 production was examined. The inhibitory effects of GSTM and AF could not be expla ined by a synergistic effect on proximal signal pathways. Conclusion. Our results demonstrate that GSTM and AF exert distinct effects on T c ell responsiveness and together synergistically inhibit mitogen induce d T cell proliferation. These results suggest the possibility that the combination of GSTM and AF may exert a heightened therapeutic effect in RA compared to the action of either agent alone.