Koh Chang-Sung
Department of Biomedical Laboratory Sciences (Neuroimmunology), Shinshu University School of Health Sciences.
Nihon Rinsho. 2003 Aug;61(8):1455-60.
Statins, 3-hydroxy-3 methylglutaryl coenzyme A(HMG-CoA) reductase inhibitors, are approved for cholesterol reduction and are commonly used to treat atherosclerosis and coronary disease. Statins may also be potent immunomodulatory agents and be beneficial in the treatment of autoimmune diseases. Statins have already been used to reduce the rejection of human heart transplants by the immune system, and there have been reports of a protective effect of injected statins in models of brain autoimmunity similar to experimental autoimmune encephalomyelitis. In vitro studies in multiple sclerosis(MS) revealed that statins reduced the expression of activation-induced adhesion molecules on T cells, modified Th1/Th2 cytokine balance, reduced matrix metalloproteinase(MMP)-9, and downregulated chemokine receptors on both B and T cells. Thus statins are effective immunomodulators in vitro that merit evaluation as treatment for MS. In vivo studies using three different animal models of MS revealed that oral atorvastatin prevented or reversed chronic and relapsing paralysis. Atorvastatin has been shown to have pleiotropic immunomodulatory effects involving both antigen presenting cells and T cell compartment. Thus, statins may be beneficial for MS, and clinical trials of the effects of statins on MS are now in progress, hopefully in a favorable way.
他汀类药物,即3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂,已被批准用于降低胆固醇,常用于治疗动脉粥样硬化和冠心病。他汀类药物也可能是强效的免疫调节剂,对自身免疫性疾病的治疗有益。他汀类药物已被用于减少免疫系统对人体心脏移植的排斥反应,并且有报道称,在类似于实验性自身免疫性脑脊髓炎的脑自身免疫模型中,注射他汀类药物具有保护作用。在多发性硬化症(MS)的体外研究中发现,他汀类药物可降低T细胞上活化诱导的黏附分子的表达,改变Th1/Th2细胞因子平衡,降低基质金属蛋白酶(MMP)-9,并下调B细胞和T细胞上的趋化因子受体。因此,他汀类药物在体外是有效的免疫调节剂,值得评估其作为MS治疗药物的效果。使用三种不同MS动物模型的体内研究表明,口服阿托伐他汀可预防或逆转慢性和复发性麻痹。阿托伐他汀已被证明具有多效性免疫调节作用,涉及抗原呈递细胞和T细胞区室。因此,他汀类药物可能对MS有益,目前关于他汀类药物对MS疗效的临床试验正在进行,有望取得良好结果。