Effects of FK506 and other immunosuppressive anti-rheumatic agents on T cell activation mediated IL-6 and IgM production in vitro
Effects of FK506 and other immunosuppressive anti-rheumatic agents on T cell activation mediated IL-6 and IgM production in vitro
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DOI：
10.1016/s1567-5769(01)00008-x
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发表时间：
2001-04-01
影响因子：
5.6
通讯作者：
Goto, T
中科院分区：
文献类型：
--
作者：
Sakuma, S;Kato, Y;Goto, T
本研究的目的是研究FK 506和其他免疫抑制剂治疗类风湿关节炎（RA）的治疗潜力，重点是对体外IL-6产生和IL-6介导的免疫应答的影响。基于T细胞在RA发病机制中起核心作用的假设，我们采用了一种通过人PBMC中T细胞活化产生IL-6的体外模型。FK 506可有效抑制抗CD 3和抗CD 28单克隆抗体（抗CD 3/CD 28）刺激的PBMC产生IL-6。环孢菌素A（CsA）也抑制抗CD 3/CD 28诱导的IL-6产生，但效力比FK 506低约100倍。地塞米松（DEX）在几乎相同的浓度下抑制抗CD 3/CD 28和LPS诱导的IL-6产生。甲氨蝶呤（MTX）不影响细胞因子的产生。抗CD 3/CD 28刺激的PBMC培养上清可促进SKW6.4细胞IgM的产生。FK 506和CsA可能通过抑制PBMC产生IgM诱导的细胞因子而抑制培养上清液诱导的IgM产生。DEX显著增强IgM的产生，尽管PBMC产生IL-6被该试剂强烈抑制。MTX对IL-6的产生无抑制作用，但能降低IgM的产生，提示FK 506对T细胞活化相关的自身免疫性疾病如RA的IL-6产生和IL-6介导的自身抗体产生的抑制作用最强。(C)2001 Elsevier Science B. V.保留所有权利。
The objective of this study was to investigate the therapeutic potential of FK506 and other immunosuppressive agents for the treatment of rheumatoid arthritis (RA), focusing on the effects on in vitro IL-6 production and IL-6-mediated immune response. We employed an in vitro model producing IL-6 via T cell activation in human PBMC, based on the hypothesis that T cells play a central role in the pathogenesis of RA. FK506 potently inhibited IL-6 production from PBMC stimulated with anti-CD3 and anti-CD28 monoclonal antibody (anti-CD3/CD28). Cyclosporin A (CsA) also inhibited the anti-CD3/CD28 induced IL-6 production but was about 100 times less potent than FK506. Dexamethasone (DEX) inhibited both anti-CD3/CD28 and LPS induced IL-6 production at almost the same concentration. Methotrexate (MTX) did not affect cytokine production. Anti-CD3/CD28 stimulated PBMC culture supernatants were found to enhance IgM production in SKW6.4 cells, The effects of anti-CD3/CD28 stimulated culture supernatants in the presence of agents on IgM production in SKW6.4 cells were investigated. FK506 and CsA led to suppression of IgM production induced by culture supernatants probably via inhibition of IgM inducible cytokine production from PBMC. DEX profoundly enhanced IgM production, although IL-6 production from PBMC was strongly inhibited by the agent. MTX decreased IgM production although it has no inhibitory effect on IL-6 production.The present study suggests that FK506 is the most effective among the four agents for the suppression of IL-6 production and IL-6-mediated autoantibody production in T cell activation related autoimmune diseases such as RA. (C) 2001 Elsevier Science B.V. All rights reserved.