Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Int Immunopharmacol. 2020 Mar;80:106138. doi: 10.1016/j.intimp.2019.106138. Epub 2020 Jan 30.
It has been shown that the blockade of chemokine receptor type 5 can dampen inflammatory reaction within the central nervous system (CNS). In the present study, we utilized maraviroc, a potent antagonist o CCR5, to examine whether this drug can mitigate neuroinflammation in the spinal cord of mice induced by experimental autoimmune encephalitis (EAE), considered a murine model of multiple sclerosis (MS). For this aim, mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55), followed by pertussis toxin to induce paralysis in EAE mice. The animals intraperitoneally received various doses of maraviroc (5, 25, and 50 mg/kg body weight) when the early clinical signs of EAE appeared. The results demonstrated that the administration of maraviroc led to a marked decrease in the clinical score and improvement in behavioral motor functions. Moreover, our finding indicated that the administration of maraviroc significantly attenuates the infiltration of inflammatory cells to the spinal cord, microgliosis, astrogliosis, pro-inflammatory cytokines, and cell death in EAE mice. The flow cytometry data indicated that a decreased number of CD4+ and CD8+ T cells in the peripheral blood of mice with EAE without affecting the number of T regulatory cells (CD4 + CD25+ forkhead box protein 3+). Finally, it seems that maraviroc is well-tolerated, and targeting CCR5 could open up a new horizon in the treatment of MS.
已经表明，阻断趋化因子受体 5 可以抑制中枢神经系统（CNS）内的炎症反应。在本研究中，我们利用马拉维若，一种有效的 CCR5 拮抗剂，来研究这种药物是否可以减轻实验性自身免疫性脑脊髓炎（EAE）诱导的小鼠脊髓中的神经炎症，EAE 被认为是多发性硬化症（MS）的一种小鼠模型。为此，我们用髓鞘少突胶质细胞糖蛋白 35-55（MOG35-55）对小鼠进行免疫，然后用百日咳毒素诱导 EAE 小鼠瘫痪。当 EAE 的早期临床症状出现时，动物通过腹腔内给予不同剂量的马拉维若（5、25 和 50mg/kg 体重）。结果表明，马拉维若的给药导致临床评分明显下降，行为运动功能得到改善。此外，我们的发现表明，马拉维若的给药显著减轻了 EAE 小鼠脊髓中炎症细胞的浸润、小胶质细胞增生、星形胶质细胞增生、促炎细胞因子和细胞死亡。流式细胞术数据表明，EAE 小鼠外周血中 CD4+和 CD8+T 细胞的数量减少，而不会影响 T 调节细胞（CD4+CD25+叉头框蛋白 3+）的数量。最后，马拉维若似乎耐受性良好，靶向 CCR5 可能为 MS 的治疗开辟新的前景。
