Captopril prevents experimental autoimmune myocarditis
Captopril prevents experimental autoimmune myocarditis
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DOI：
10.4049/jimmunol.171.1.346
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发表时间：
2003-07-01
影响因子：
4.4
通讯作者：
Engman, DM
中科院分区：
文献类型：
--
作者：
Godsel, LM;Leon, JS;Engman, DM
卡托普利是一种血管紧张素转换酶抑制剂，广泛用于治疗多种心肌病，但其对自身免疫性心肌炎的作用尚未得到实验证实。我们研究了卡托普利对肌球蛋白诱导的实验性自身免疫性心肌炎的影响。用同源心肌肌球蛋白免疫的 A/J 小鼠在饮用水中加入 75 mg/L 卡托普利。卡托普利显着降低了心肌炎的发生率和严重程度，同时降低了心脏重量与体重的比率和心脏重量。卡托普利特异性干扰细胞介导的免疫，因为肌球蛋白迟发型超敏反应 (DTH) 降低，而抗肌球蛋白抗体的产生不受影响。卡托普利治疗的 OVA 免疫小鼠也表现出 OVA DTH 的减少。在肌球蛋白免疫、未经治疗的小鼠中，直接向测试部位注射卡托普利也抑制了肌球蛋白 DTH。有趣的是，卡托普利不会直接影响 Ag 特异性 T 细胞反应性，因为体内和体外卡托普利治疗都不影响 Ag 刺激的培养脾细胞的增殖、IFN-γ 分泌或 IL-2 分泌。这些结果表明卡托普利可改善实验性自身免疫性心肌炎，并且可能至少部分通过干扰细胞募集到炎症部位和局部炎症环境来发挥作用。
Captopril, an angiotensin-converting enzyme inhibitor, is widely used in the treatment of a variety of cardiomyopathies, but its effect on autoimmune myocarditis has not been addressed experimentally. We investigated the effect of captopril on myosin-induced experimental autoimmune myocarditis. A/J mice, immunized with syngeneic cardiac myosin, were given 75 mg/L of captopril in their drinking water. Captopril dramatically reduced the incidence and severity of myocarditis, which was accompanied by a reduction in heart weight to body weight ratio and heart weight. Captopril specifically interfered with cell-mediated immunity as myosin delayed-type hypersensitivity (DTH) was reduced, while anti-myosin Ab production was not affected. Captopril-treated, OVA-immunized mice also exhibited a decrease in OVA DTH. In myosin-immunized, untreated mice, injection of captopril directly into the test site also suppressed myosin DTH. Interestingly, captopril did not directly affect Ag-specific T cell responsiveness because neither in vivo nor in vitro captopril treatment affected the proliferation, IFN-gamma secretion, or IL-2 secretion by Ag-stimulated cultured splenocytes. These results indicate that captopril ameliorates experimental autoimmune myocarditis and may act, at least in part, by interfering with the recruitment of cells to sites of inflammation and the local inflammatory environment.