Statins as immunomodulators -: Comparison with interferon-β1b in MS
Statins as immunomodulators -: Comparison with interferon-β1b in MS
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DOI：
10.1212/wnl.59.7.990
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发表时间：
2002-10-08
期刊：
影响因子：
9.9
通讯作者：
Archelos, JJ
中科院分区：
文献类型：
--
作者：
Neuhaus, O;Strasser-Fuchs, S;Archelos, JJ
背景：最近的数据表明，他汀类药物可能是有效的免疫调节剂。为了评价他汀类药物作为免疫调节剂在MS中的潜在作用，作者研究了其体外免疫作用，并将其与干扰素（IFN）β-1b进行了比较。研究方法：在洛伐他汀、辛伐他汀、美伐他汀、IFN β-1b或他汀类药物加IFN β-1b的情况下，用伴刀豆球蛋白A、植物血凝素或CD 3抗体刺激从未治疗或IFN β-1治疗的复发缓解型MS患者或健康供体（HD）获得的外周血单核细胞（PBMC）和T细胞。作者分析了T细胞和B细胞的增殖活性、细胞因子的产生和释放、基质金属蛋白酶（MMP）的活性以及T细胞和B细胞上活化标志物、粘附分子和趋化因子受体的表面表达。结果如下：所有三种他汀类药物均以剂量依赖性方式抑制刺激的PBMC增殖，其中辛伐他汀最有效，其次是洛伐他汀和美伐他汀。IFN β-1b显示出类似的作用;他汀类药物和IFN β-1b一起增加了它们的抑制潜力。此外，他汀类药物减少活化诱导的粘附分子在T细胞上的表达，改变T辅助细胞LIT辅助细胞2细胞因子平衡，减少MMP-9，下调B和T细胞上的趋化因子受体。他汀类药物除了具有较强的抗炎作用外，还具有一定的促炎作用。结论：他汀类药物是有效的免疫调节剂，在体外，值得评估作为治疗MS。
Background: Recent data suggest that statins may be potent immunomodulatory agents. In order to evaluate the potential role of statins as immunomodulators in MS, the authors studied their immunologic effects in vitro and compared them to interferon (IFN)beta-1b. Methods: Peripheral blood mononuclear cells (PBMC) obtained from untreated or IFNbeta-1-treated patients with relapsing-remitting MS or from healthy donors (HD) and T cells were stimulated with concanavalin A, phytohemagglutinin, or antibody to CD3 in the presence of lovastatin, sinivastatin, mevastatin, IFNbeta-1b, or statins plus IFNbeta-1b. The authors analyzed proliferative activity of T cells and B cells, cytokine production and release, activity of matrix metalloproteinases (MMP), and surface expression of activation markers, adhesion molecules, and chemokine receptors on both T and B cells. Results: All three statins inhibited proliferation of stimulated PBMC in a dose-dependent manner, with simvastatin being the most potent, followed by lovastatin and mevastatin. IFNbeta-1b showed a similar effect; statins and IFNbeta-1b together added their inhibitory potentials. Furthermore, statins reduced the expression of activation-induced adhesion molecules on T cells, modified the T helper LIT helper 2 cytokine balance, reduced MMP-9, and downregulated chemokine receptors on both B and T cells. Besides strong anti-inflammatory properties, statins also exhibited some proinflammatory effects. Conclusions: Statins are effective immunomodulators in vitro that merit evaluation as treatment for MS.