Russell G, Graveley R, Seid J, al-Humidan A K, Skjodt H
Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, England.
Semin Arthritis Rheum. 1992 Jun;21(6 Suppl 3):16-22. doi: 10.1016/0049-0172(92)90009-3.
Cyclosporine is a potent immunomodulatory agent with an increasing number of clinical applications. Its major mode of action is inhibition of the production of cytokines involved in the regulation of T-cell activation. In particular, cyclosporine inhibits the transcription of interleukin 2. Although cyclosporine's major actions are on T cells, there is some evidence that it produces direct effects on other cell types. Its immunosuppressive action is closely linked to its binding of cyclophilin, a member of a family of high-affinity cyclosporine-binding proteins widely distributed in different cell types and in different species. The cyclophilins have been shown to have peptidyl-prolyl cis-trans isomerase enzyme activity that is blocked by cyclosporine. Although this may be a factor in cyclosporine's selective inhibition of cytokine gene transcription, it is still unclear whether inhibition of this activity is the mechanism through which cyclosporine exerts its effects on target cells. The ubiquitous presence of cyclophilins raises the question of why cyclosporine has major effects on T cells. Perhaps the critical proteins affected are transcriptional regulators restricted in their tissue distribution. The effects of cyclosporine on T cells and, directly or indirectly, on connective tissue cells, all of which can produce a range of cytokines, are of interest in relation to the tissue changes that occur in such inflammatory conditions as rheumatoid arthritis.
环孢素是一种具有越来越多临床应用的强效免疫调节剂。其主要作用方式是抑制参与调节T细胞活化的细胞因子的产生。特别是，环孢素抑制白细胞介素2的转录。虽然环孢素的主要作用是作用于T细胞，但有一些证据表明它对其他细胞类型有直接影响。其免疫抑制作用与其与亲环蛋白的结合密切相关，亲环蛋白是一类高亲和力环孢素结合蛋白家族的成员，广泛分布于不同细胞类型和不同物种中。已证明亲环蛋白具有肽基脯氨酰顺反异构酶活性，该活性被环孢素阻断。虽然这可能是环孢素选择性抑制细胞因子基因转录的一个因素，但仍不清楚抑制这种活性是否是环孢素对靶细胞发挥作用的机制。亲环蛋白的普遍存在提出了一个问题，即为什么环孢素对T细胞有主要影响。也许受影响的关键蛋白质是组织分布受限的转录调节因子。环孢素对T细胞以及直接或间接对结缔组织细胞的影响，所有这些细胞都能产生一系列细胞因子，与类风湿性关节炎等炎症性疾病中发生的组织变化有关，因此备受关注。
