Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, 115 Ximen Street, Kaifeng, 475000, China.
School of Medicine, Nankai University, Tianjin, 300071, China.
Inflammation. 2023 Oct;46(5):1626-1638. doi: 10.1007/s10753-023-01829-y. Epub 2023 May 25.
Multiple sclerosis (MS), a T-cell-mediated autoimmune disease that affects the central nervous system (CNS), is characterized by white matter demyelination, axon destruction, and oligodendrocyte degeneration. Ivermectin, an anti-parasitic drug, has anti-inflammatory, anti-tumor, and antiviral properties. However, to date, there are no in-depth studies on the effect of ivermectin on the function effector of T cells in murine experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Here, we conducted in vitro experiments and found that ivermectin inhibited the proliferation of total T cells (CD3) and their subsets (CD4 and CD8 T cells) as well as T cells secreting the pro-inflammatory cytokines IFN-γ and IL-17A; ivermectin also increased IL-2 production and IL-2Rα (CD25) expression, which was accompanied by an increase in the frequency of CD4CD25Foxp3 regulatory T cells (Treg). Importantly, ivermectin administration reduced the clinical symptoms of EAE mice by preventing the infiltration of inflammatory cells into the CNS. Additional mechanisms showed that ivermectin promoted Treg cells while inhibiting pro-inflammatory Th1 and Th17 cells and their IFN-γ and IL-17 secretion; ivermectin also upregulated IL-2 production from MOG-stimulated peripheral lymphocytes. Finally, ivermectin decreased IFN-γ and IL-17A production and increased IL-2 level, CD25 expression, and STAT5 phosphorylation in the CNS. These results reveal a previously unknown etiopathophysiological mechanism by which ivermectin attenuates the pathogenesis of EAE, indicating that it may be a promising option for T-cell-mediated autoimmune diseases such as MS.
多发性硬化症（MS）是一种 T 细胞介导的自身免疫性疾病，影响中枢神经系统（CNS），其特征是白质脱髓鞘、轴突破坏和少突胶质细胞变性。伊维菌素是一种抗寄生虫药物，具有抗炎、抗肿瘤和抗病毒特性。然而，迄今为止，尚无关于伊维菌素对实验性自身免疫性脑脊髓炎（EAE），即 MS 动物模型中 T 细胞功能效应器的影响的深入研究。在这里，我们进行了体外实验，发现伊维菌素抑制总 T 细胞（CD3）及其亚群（CD4 和 CD8 T 细胞）以及分泌促炎细胞因子 IFN-γ和 IL-17A 的 T 细胞的增殖；伊维菌素还增加了 IL-2 的产生和 IL-2Rα（CD25）的表达，同时增加了 CD4CD25Foxp3 调节性 T 细胞（Treg）的频率。重要的是，伊维菌素通过防止炎症细胞浸润中枢神经系统来减轻 EAE 小鼠的临床症状。额外的机制表明，伊维菌素促进 Treg 细胞，同时抑制促炎 Th1 和 Th17 细胞及其 IFN-γ和 IL-17 的分泌；伊维菌素还上调了 MOG 刺激的外周淋巴细胞中 IL-2 的产生。最后，伊维菌素降低了 IFN-γ和 IL-17A 的产生，增加了 IL-2 水平、CD25 表达和 CNS 中的 STAT5 磷酸化。这些结果揭示了伊维菌素减轻 EAE 发病机制的一个以前未知的病因发病机制，表明它可能是一种有前途的选择，用于治疗 MS 等 T 细胞介导的自身免疫性疾病。
