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螺锗的抗关节炎和免疫调节活性。

Antiarthritic and immunoregulatory activity of spirogermanium.

作者信息

DiMartino M J, Lee J C, Badger A M, Muirhead K A, Mirabelli C K, Hanna N

出版信息

J Pharmacol Exp Ther. 1986 Jan;236(1):103-10.

PMID:2934544
Abstract

Spirogermanium is a novel metal containing azaspirane compound with reported antitumor activity. The results of the present investigation demonstrate that spirogermanium also exhibits antiarthritic and immunoregulatory activities after p.o. administration to rats. Spirogermanium decreased hindleg inflammatory lesions of adjuvant arthritic rats when administered p.o. before or after the development of the arthritic lesions. After termination of spirogermanium administration, the adjuvant-injected hindleg lesions remained significantly suppressed for at least 2 weeks postdrug treatment; whereas, the uninjected, immune-mediated hindleg inflammation tended to increase postdrug treatment. In multiparameter ex vivo studies, untreated arthritic rats exhibited enhanced cyanine dye fluorescence in peripheral blood monocytes, enhanced interleukin (IL)-1 production by adherent spleen cells and depressed IL-2 and IL-3 production by splenic lymphocytes. Spirogermanium normalized these changes to various degrees, with the exception of the depressed IL-2 and IL-3 production. Spirogermanium administered to normal nonarthritic rats decreased mitogenic responses of spleen cells to Concanavalin A which was found to be caused, at least in part, by enhanced suppressor cell activity. The antiarthritic and immunoregulatory profile of spirogermanium appeared to be different from the profiles of the antiarthritic agents, auranofin and indomethacin.

摘要

螺锗是一种新型的含金属氮杂螺环化合物,据报道具有抗肿瘤活性。本研究结果表明,给大鼠口服螺锗后,它还表现出抗关节炎和免疫调节活性。在佐剂性关节炎大鼠关节炎病变出现之前或之后口服给药时,螺锗可减轻其后腿的炎症损伤。停止给予螺锗后,在停药后至少2周内,注射佐剂的后腿损伤仍受到显著抑制;而未注射的、由免疫介导的后腿炎症在停药后则有加重趋势。在多参数体外研究中,未经治疗的关节炎大鼠外周血单核细胞中的花青染料荧光增强,贴壁脾细胞产生白细胞介素(IL)-1增多,脾淋巴细胞产生IL-2和IL-3减少。除了IL-2和IL-3产生减少外,螺锗在不同程度上使这些变化恢复正常。给正常的非关节炎大鼠口服螺锗可降低脾细胞对刀豆球蛋白A的促有丝分裂反应,这至少部分是由抑制细胞活性增强所致。螺锗的抗关节炎和免疫调节特性似乎与抗关节炎药物金诺芬和吲哚美辛不同。

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