Neuhaus Oliver, Stüve Olaf, Archelos Juan J, Hartung Hans-Peter
Department of Neurology, Heinrich Heine University, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
J Neurol Sci. 2005 Jun 15;233(1-2):173-7. doi: 10.1016/j.jns.2005.03.030. Epub 2005 Apr 20.
Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and are widely prescribed as cholesterol-lowering agents. They are promising candidates for future treatment in multiple sclerosis (MS) as they have been shown to exhibit immunomodulatory effects. Recent reports have demonstrated that statins are effective in preventing and reversing chronic and relapsing experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Furthermore, in vitro experiments with human immune cells have documented an immunomodulatory mode of action of statins comparable to that of interferon (IFN)-beta. An open label clinical trial assessing simvastatin in MS revealed a significant decrease in the number and volume of new MRI lesions and a favourable safety profile. This article reviews data thus far present on the putative mechanisms of action of statins in the immunopathogenesis of MS. Furthermore, the role of statins as potential pharmacotherapy for MS is discussed in the context of the mechanisms of approved immunotherapies in MS, namely IFN-beta and glatiramer acetate (GA).
他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶的抑制剂，被广泛用作降胆固醇药物。由于已显示出具有免疫调节作用，它们是未来治疗多发性硬化症（MS）的有前景的候选药物。最近的报告表明，他汀类药物在预防和逆转慢性复发性实验性自身免疫性脑脊髓炎（EAE，一种MS的动物模型）方面是有效的。此外，用人免疫细胞进行的体外实验记录了他汀类药物与干扰素（IFN）-β相当的免疫调节作用模式。一项评估辛伐他汀治疗MS的开放标签临床试验显示，新的MRI病变数量和体积显著减少，且安全性良好。本文综述了迄今为止有关他汀类药物在MS免疫发病机制中假定作用机制的数据。此外，在MS中已批准的免疫疗法（即IFN-β和醋酸格拉替雷（GA））的作用机制背景下，讨论了他汀类药物作为MS潜在药物治疗的作用。
