Laboratories of Immunobiology and Molecular Immunology, Rega Institute for Medical Research, K.U. Leuven, B-3000 Leuven, Belgium.
Cytokine Growth Factor Rev. 2011 Oct-Dec;22(5-6):359-65. doi: 10.1016/j.cytogfr.2011.11.005. Epub 2011 Nov 25.
Multiple sclerosis (MS) is an autoimmune disease with a spectrum of clinical evolutions. We here summarize recent insights into the neuroinflammatory processes of demyelination, vascular cuffing, destruction of the blood brain barrier (BBB), neuronal toxicity and the ensuing (re)activation of autoreactive lymphocytes. Translation of these processes in molecular terms indicates that cytokines, including interferons, ligands of the tumor necrosis factor receptor family and interleukins, and also chemokines and matrix metalloproteinases play pivotal roles in MS. This not only helps to understand disease mechanisms in the central nervous system of affected patients, but also forms a solid scientific basis to improve present therapies. Treatment of MS with parenterally administered anti-inflammatory agents may be improved, based on present knowledge and new insights obtained with animal models. Such innovations include better use of knowledge about the formulation, administration, turnover and glycosylation of interferon-β (IFN-β), combinations of IFN-β with inhibitors of IFN-β-degrading proteinases in MS, and new ways to diminish vascular cuffs and the transmigration of leukocytes across the two basement membranes of the BBB. Novel molecules interfering with matrix metalloproteinases and chemokines, such as EMMPRIN, COAM and monoclonal antibodies are currently being investigated, demonstrating continued efforts to find new drugs for MS treatment.
多发性硬化症（MS）是一种自身免疫性疾病，具有多种临床演变。我们在这里总结了对脱髓鞘、血管套形成、血脑屏障（BBB）破坏、神经元毒性以及随后自身反应性淋巴细胞激活的神经炎症过程的最新见解。这些过程的分子翻译表明，细胞因子，包括干扰素、肿瘤坏死因子受体家族配体和白细胞介素，以及趋化因子和基质金属蛋白酶在 MS 中起关键作用。这不仅有助于了解受影响患者中枢神经系统中的疾病机制，而且为改善现有治疗方法提供了坚实的科学基础。基于目前的知识和从动物模型中获得的新见解，用注射用抗炎药物治疗 MS 可能会得到改善。这些创新包括更好地利用关于干扰素-β（IFN-β）的制剂、给药、周转率和糖基化的知识，在 MS 中使用 IFN-β与 IFN-β 降解蛋白酶抑制剂的组合，以及减少血管套和白细胞穿过 BBB 的两个基底膜迁移的新方法。目前正在研究干扰基质金属蛋白酶和趋化因子的新型分子，如 EMMPRIN、COAM 和单克隆抗体，这表明人们一直在努力寻找治疗 MS 的新药。
