Hashimoto K, Whitehurst C E, Lipsky P E
Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
J Rheumatol. 1994 Jun;21(6):1020-6.
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 thiomalate; GSTM) and orally active gold (auranofin; AF).
The effects of GSTM and AF on in vitro models of human T cell activation were examined.
GSTM and AF were found to exert a synergistic inhibitory effect on human T lymphocyte proliferation in vitro. The concentrations of GSTM and AF that synergistically inhibit T cell proliferation were easily attainable in the serum or synovium of patients treated with 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 explained by a synergistic effect on proximal signal pathways.
Our results demonstrate that GSTM and AF exert distinct effects on T cell responsiveness and together synergistically inhibit mitogen induced 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.
金化合物作为类风湿关节炎（RA）的治疗药物已应用多年，但其作用的分子机制尚不清楚。我们开展研究以比较胃肠外金（硫代苹果酸金钠；GSTM）和口服活性金（金诺芬；AF）的免疫抑制活性。
检测GSTM和AF对人T细胞活化体外模型的影响。
发现GSTM和AF在体外对人T淋巴细胞增殖发挥协同抑制作用。在接受这些药物治疗的患者的血清或滑膜中，可轻易达到协同抑制T细胞增殖的GSTM和AF浓度。检测白细胞介素2（IL-2）受体表达或IL-2产生时，GSTM和AF的协同抑制作用不明显。GSTM和AF的抑制作用无法用对近端信号通路的协同作用来解释。
我们的结果表明，GSTM和AF对T细胞反应性发挥不同作用，并共同协同抑制丝裂原诱导的T细胞增殖。这些结果提示，与单独使用任一药物相比，GSTM和AF联合使用可能在RA中发挥更强的治疗作用。
