INSERM UMR1163 and CNRS URL 8254, Imagine Institute, Paris, France.
Paris Descartes University-Sorbonne Paris Cité, Paris, France.
Front Immunol. 2019 Mar 28;10:588. doi: 10.3389/fimmu.2019.00588. eCollection 2019.
Cyclosporin-A has been known and used for a long time, since its "fast track" approval in the early 80's. This molecule has rapidly demonstrated unexpected immunosuppressive properties, transforming the history of organ transplantation. Cyclosporin's key effect relies on modulation on T-lymphocyte activity, which explains its role in the prevention of graft rejection. However, whether cyclosporin-A exerts other effects on immune system remains to be determined. Until recently, cyclosporin-A was mainly used at a high-dose, but given the drug toxicity and despite the fear of losing its immunosuppressive effects, there is nowadays a tendency to decrease its dose. The literature has been reporting data revealing a paradoxical effect of low dosage of cyclosporin-A. These low-doses appear to have immunomodulatory properties, with different effects from high-doses on CD8+ T lymphocyte activation, auto-immune diseases, graft-vs.-host disease and cancer. The aim of this review is to discuss the role of cyclosporin-A, not only as a consecrated immunosuppressive agent, but also as an immunomodulatory drug when administrated at low-dose. The use of low-dose cyclosporin-A may become a new therapeutic strategy, particularly to treat cancer.
环孢素 A 已经为人熟知并应用多年，自 20 世纪 80 年代初的“快速通道”批准以来。这种分子迅速显示出出乎意料的免疫抑制特性，改变了器官移植的历史。环孢素的关键作用依赖于 T 淋巴细胞活性的调节，这解释了它在预防移植物排斥中的作用。然而，环孢素 A 是否对免疫系统有其他影响仍有待确定。直到最近，环孢素 A 主要以高剂量使用，但由于药物毒性，尽管担心失去其免疫抑制作用，现在有降低剂量的趋势。文献报告的数据揭示了低剂量环孢素 A 的矛盾作用。这些低剂量似乎具有免疫调节特性，对 CD8+T 淋巴细胞激活、自身免疫性疾病、移植物抗宿主病和癌症的影响与高剂量不同。本综述的目的是讨论环孢素 A 的作用，不仅作为一种既定的免疫抑制剂，而且在低剂量时作为一种免疫调节药物。低剂量环孢素 A 的使用可能成为一种新的治疗策略，特别是用于治疗癌症。
