Division of Pathological Science, Department of Clinical Pharmacology, Kyoto Pharmaceutical University, 5 Misasagi Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan.
Cardiovasc Res. 2010 Aug 1;87(3):424-30. doi: 10.1093/cvr/cvq078. Epub 2010 Mar 7.
The plasma level of interleukin-6 (IL-6) has been reported to be associated with left ventricular (LV) remodelling after myocardial infarction (MI). The present study was designed to examine whether anti-IL-6 receptor antibody (MR16-1) prevents the development of LV remodelling after MI.
Balb/c male mice were subjected to MI by ligating the left anterior descending coronary artery. The mice were then treated with an intraperitoneal injection of MR16-1 (500 microg/body) or control IgG. MR16-1 decreased the myocardial myeloperoxidase activity and monocyte chemoattractant protein-1 concentration in the infarct region, concomitant with decreases in neutrophil and macrophage infiltration 3 days after ligation, while infarct size was comparable between the control IgG- and MR16-1-treated mice. At 7 days after ligation, MR16-1 significantly suppressed matrix metalloproteinase-2 activity in the infarct region. Furthermore, the MR16-1-treated mice demonstrated a reduction in LV dilatation and an improvement in LV contractile function compared with the control IgG-treated mice at 7 and 28 days after surgery, leading to an improvement in survival rate (80.6 vs. 59.5%, P < 0.05) at 28 days after surgery. The beneficial effects of MR16-1 were accompanied by histological suppression of cardiomyocyte hypertrophy and interstitial fibrosis in the non-infarct region.
Administration of MR16-1 after MI suppressed myocardial inflammation, resulting in the amelioration of LV remodelling. Neutralization of the IL-6 receptor is a potentially useful strategy for protecting hearts from LV remodelling after MI.
已有研究报道，白细胞介素-6（IL-6）的血浆水平与心肌梗死后的左心室（LV）重构有关。本研究旨在探讨抗 IL-6 受体抗体（MR16-1）是否能预防心肌梗死后 LV 重构的发生。
Balb/c 雄性小鼠通过结扎左前降支冠状动脉造成心肌梗死。然后，通过腹腔注射 MR16-1（500μg/只）或对照 IgG 对小鼠进行治疗。MR16-1 降低了梗塞区域的心肌髓过氧化物酶活性和单核细胞趋化蛋白-1 浓度，同时还降低了 3 天后的中性粒细胞和巨噬细胞浸润，而梗塞面积在对照 IgG 和 MR16-1 治疗组之间无差异。在结扎后 7 天，MR16-1 显著抑制了梗塞区域的基质金属蛋白酶-2 活性。此外，与对照 IgG 治疗组相比，MR16-1 治疗组在手术后 7 天和 28 天左心室扩张减少，左心室收缩功能改善，导致手术后 28 天的存活率提高（80.6%比 59.5%，P<0.05）。MR16-1 的有益作用伴随着梗塞区域外的心肌细胞肥大和间质纤维化的组织学抑制。
心肌梗死后给予 MR16-1 可抑制心肌炎症，从而改善 LV 重构。IL-6 受体的中和可能是一种保护心脏免受心肌梗死后 LV 重构的有用策略。
