Department of Pathogen Biology and Immunology, Logistics University of the Chinese People's Armed Police Force, Tianjin, People's Republic of China.
Int Immunopharmacol. 2013 Jun;16(2):306-12. doi: 10.1016/j.intimp.2013.03.011. Epub 2013 Apr 11.
Artemisinin and its derivatives have been reported to have immunosuppressive activity in some laboratory studies. However, the detail of mechanism remains to be demonstrated. The objective of this study is to clarify the immunosuppressive activity of artesunate (AST), one kind of artemisinin derivatives, and to find its unexplored mode of action. In vitro, the proliferation of T lymphocytes and its cytotoxicity were measured by WST-1 and MTT assay. In vivo, the immunomodulatory effect of AST was evaluated in a mouse model of delayed type hypersensitivity reaction (DTH), which was based on a T cell-mediated immune response. The data displayed that AST had a relatively high immunosuppressive activity with low toxicity, and could inhibit T lymphocyte proliferation induced by mitogen and alloantigen. Meanwhile, topical administration of AST could suppress DTH response significantly. Moreover, AST could also increase the secretion of TFG-β, coupling with the striking enhance of NF-κB/p65 and Smad2/3 signaling. The promotion of CD4(+)CD25(+) regulatory T cells (Tregs) was shown to be a possible mechanism involved in AST-mediated regulation. Taken together, these observations exhibit the potential of developing AST as a novel safe remedy for the treatment of T cell-mediated immune disorders.
青蒿素及其衍生物在一些实验室研究中被报道具有免疫抑制活性。然而，其详细机制仍有待证明。本研究旨在阐明青蒿琥酯（AST）作为一种青蒿素衍生物的免疫抑制活性，并寻找其未被探索的作用模式。在体外，通过 WST-1 和 MTT 测定法测量 T 淋巴细胞的增殖及其细胞毒性。在体内，基于 T 细胞介导的免疫反应，在迟发型超敏反应（DTH）小鼠模型中评估 AST 的免疫调节作用。数据显示，AST 具有相对较高的免疫抑制活性和低毒性，可抑制有丝分裂原和同种抗原诱导的 T 淋巴细胞增殖。同时，AST 的局部给药可显著抑制 DTH 反应。此外，AST 还可以增加 TGF-β的分泌，与 NF-κB/p65 和 Smad2/3 信号的显著增强相关。显示 CD4(+)CD25(+)调节性 T 细胞（Tregs）的促进可能是 AST 介导调节的一种可能机制。总之，这些观察结果表明开发 AST 作为治疗 T 细胞介导的免疫紊乱的新型安全疗法的潜力。
