Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, People's Republic of China.
J Surg Res. 2013 Dec;185(2):912-22. doi: 10.1016/j.jss.2013.06.057. Epub 2013 Jul 22.
In addition to achieving a balance between the positive (controlling rejection) and the negative (infection and malignancy) aspects of drug-induced immunodeficiency, new immunosuppressive combinations must address the issue of nonimmune drug toxicity that may be dose limiting. Cordycepin is a type of adenosine analog extracted from Cordyceps militaris. In the present study, we investigated its immunosuppressive effect on T cell both in vitro and in vivo.
We evaluated the effects of cordycepin on concanavalin A-induced production of immune mediators in mouse splenocyte by enzyme-linked immunosorbent assay and flow cytometry. Furthermore, using Western blotting, we studied signal transduction mechanisms to determine how cordycepin inhibited T-cell activation in purified mouse T lymphocytes. To confirm the immunosuppressive activity of cordycepin in vivo, we induced the T cell-mediated delayed-type hypersensitivity reaction in a 2,4-dinitro-1-fluorobenzene-induced mouse model.
The in vitro results showed that cordycepin markedly suppressed concanavalin A-induced splenocyte proliferation, Th1 and Th2 cytokine production, and the ratio of CD4(+)-to-CD8(+) T cells. The administration of cordycepin in vivo markedly suppressed the T cell-mediated delayed-type hypersensitivity reaction. The data revealed that cordycepin effectively shocked the nuclear factor kappa B and nuclear factor of activated T cells 2 signal transduction pathways but had no effect on the mitogen activated protein kinase signal transduction pathway.
These observations indicated that cordycepin has a potential role in downregulating the immune system and could be developed as a useful immunosuppressive agent for treating undesired immune responses.
除了在药物诱导免疫缺陷的积极方面（控制排斥反应）和消极方面（感染和恶性肿瘤）之间取得平衡外，新的免疫抑制组合还必须解决可能具有剂量限制的非免疫药物毒性问题。蛹虫草素是从蛹虫草中提取的一种腺苷类似物。在本研究中，我们研究了它对 T 细胞的体外和体内免疫抑制作用。
我们通过酶联免疫吸附试验和流式细胞术评估了蛹虫草素对刀豆蛋白 A 诱导的小鼠脾细胞免疫介质产生的影响。此外，我们使用 Western blot 研究了信号转导机制，以确定蛹虫草素如何抑制纯化的小鼠 T 淋巴细胞的 T 细胞活化。为了确认蛹虫草素在体内的免疫抑制活性，我们在 2,4-二硝基-1-氟苯诱导的小鼠模型中诱导 T 细胞介导的迟发型超敏反应。
体外结果表明，蛹虫草素显著抑制刀豆蛋白 A 诱导的脾细胞增殖、Th1 和 Th2 细胞因子产生以及 CD4(+)-与 CD8(+) T 细胞的比值。体内给予蛹虫草素显著抑制 T 细胞介导的迟发型超敏反应。数据显示，蛹虫草素有效地抑制了核因子 κB 和活化 T 细胞核因子 2 信号转导途径，但对丝裂原激活蛋白激酶信号转导途径没有影响。
这些观察结果表明，蛹虫草素具有下调免疫系统的潜力，可开发为治疗不良免疫反应的有用免疫抑制剂。
