Kermani-Arab V, Salehmoghaddam S, Danovitch G, Hirji K, Rezai A
Transplantation. 1985 Apr;39(4):439-42. doi: 10.1097/00007890-198504000-00019.
Normal human peripheral blood mononuclear cells (PBMC) were cultured with phytohemagglutinin-P (PHAP) and cyclosporine (CsA) to investigate the mode of action of CsA on cellular proliferation. CsA at 1 microgram/ml exerted a marked inhibitory effect on PBMC responsiveness to PHAP. An antiproliferative effect of CsA was observed at the inductive phase of the cell cycle, but the drug was ineffective when it was added to cultures 24 hr after stimulation. In parallel with this inhibitory effect interleukin 2 (IL-2) production was inhibited. In contrast, IL-2 receptor was expressed on the CsA-treated cells, and the antiproliferative influence of the drug was completely reversed by addition of highly purified human IL-2 to the CsA-treated cells. Exogenous IL-2, however, did not restore cellular capacity to produce IL-2. This study suggests that CsA acts by inhibiting IL-2 production (via blockade of IL-2 gene expression) rather than by preventing the expression of the IL-2 receptor.
用人外周血单个核细胞（PBMC）与植物血凝素-P（PHAP）及环孢素（CsA）共同培养，以研究CsA对细胞增殖的作用方式。浓度为1微克/毫升的CsA对PBMC对PHAP的反应性有显著抑制作用。在细胞周期的诱导期观察到CsA有抗增殖作用，但在刺激后24小时将药物加入培养物中则无效。与这种抑制作用同时，白细胞介素2（IL-2）的产生也受到抑制。相反，IL-2受体在经CsA处理的细胞上表达，并且通过向经CsA处理的细胞中加入高度纯化的人IL-2，药物的抗增殖作用被完全逆转。然而，外源性IL-2并不能恢复细胞产生IL-2的能力。本研究提示，CsA的作用机制是抑制IL-2的产生（通过阻断IL-2基因表达），而不是阻止IL-2受体的表达。
