Weber M S, Zamvil S S
Department of Neurology, University of California, San Francisco, 513 Parnassus Avenue, S-268, San Francisco, CA 94143-0435, USA.
Curr Top Microbiol Immunol. 2008;318:313-24. doi: 10.1007/978-3-540-73677-6_12.
Statins are inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, which are widely prescribed for their cholesterol-lowering properties in order to reduce atherogenesis and cardiovascular morbidity. Moreover, statins have been shown to exert pleiotropic immunomodulatory effects that might be of therapeutic benefit in autoimmune disorders. Statins appear to alter immune function largely independent of lipid lowering and rather through inhibition of posttranslational protein prenylation of small regulatory GTP-binding proteins. In experimental autoimmune encephalomyelitis (EAE), the murine model for multiple sclerosis (MS), statins were shown to reverse established paralysis and to exert synergistic benefit in combination with agents approved for MS therapy. Based upon these encouraging findings in treatment of EAE, statins are now being tested in clinical trials in patients with MS.
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,因其降低胆固醇的特性而被广泛处方,以减少动脉粥样硬化的发生和心血管疾病的发病率。此外,他汀类药物已被证明具有多效性免疫调节作用,这可能对自身免疫性疾病具有治疗益处。他汀类药物似乎在很大程度上独立于降低血脂来改变免疫功能,而是通过抑制小的调节性GTP结合蛋白的翻译后蛋白质异戊二烯化来实现。在实验性自身免疫性脑脊髓炎(EAE)(多发性硬化症(MS)的小鼠模型)中,他汀类药物被证明可以逆转已有的瘫痪,并与批准用于MS治疗的药物联合使用时发挥协同作用。基于这些在EAE治疗中令人鼓舞的发现,他汀类药物目前正在MS患者的临床试验中进行测试。