Department of Neurology, Dartmouth Hitchcock Medical Center (DHMC), Geisel School of Medicine, Lebanon, NH, 03756, USA.
Department of Neurology, University of Medicine and Dentistry-New Jersey Medical School, Newark, NJ, USA.
J Neurovirol. 2017 Dec;23(6):825-838. doi: 10.1007/s13365-017-0570-8. Epub 2017 Sep 14.
Teriflunomide is an oral therapy approved for the treatment of relapsing remitting multiple sclerosis (MS), showing both anti-inflammatory and antiviral properties. Currently, it is uncertain whether one or both of these properties may explain teriflunomide's beneficial effect in MS. Thus, to learn more about its mechanisms of action, we evaluated the effect of teriflunomide in the Theiler's encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model, which is both a viral infection and an excellent model of the progressive disability of MS. We assessed the effects of the treatment on central nervous system (CNS) viral load, intrathecal immune response, and progressive neurological disability in mice intracranially infected with TMEV. In the TMEV-IDD model, we showed that teriflunomide has both anti-inflammatory and antiviral properties, but there seemed to be no impact on disability progression and intrathecal antibody production. Notably, benefits in TMEV-IDD were mostly mediated by effects on various cytokines produced in the CNS. Perhaps the most interesting result of the study has been teriflunomide's antiviral activity in the CNS, indicating it may have a role as an antiviral prophylactic and therapeutic compound for CNS viral infections.
特立氟胺是一种口服治疗药物，已获准用于治疗复发缓解型多发性硬化症（MS），具有抗炎和抗病毒特性。目前尚不清楚这些特性中的一种或两种是否可以解释特立氟胺对 MS 的有益作用。因此，为了更多地了解其作用机制，我们评估了特立氟胺在 Theiler 脑炎病毒诱导的脱髓鞘疾病（TMEV-IDD）模型中的作用，该模型既是病毒感染，也是 MS 进行性残疾的优秀模型。我们评估了特立氟胺治疗对经颅内感染 TMEV 的小鼠中枢神经系统（CNS）病毒载量、鞘内免疫反应和进行性神经功能障碍的影响。在 TMEV-IDD 模型中，我们表明特立氟胺具有抗炎和抗病毒特性，但似乎对残疾进展和鞘内抗体产生没有影响。值得注意的是，TMEV-IDD 中的益处主要是通过对 CNS 中产生的各种细胞因子的影响来介导的。该研究最有趣的结果是特立氟胺在 CNS 中的抗病毒活性，表明它可能作为 CNS 病毒感染的抗病毒预防和治疗性化合物发挥作用。
