Abstract 960: Antagonism of Interleukin-6 Receptor Attenuates Cardiac Remodeling After Myocardial Infarction
[Purpose] Circulating level of interleukin-6 (IL-6) has been reported to associated with cardiac remodeling after myocardial infarction (MI). This study was designed to determine whether anti-IL-6 receptor antibody (MR16–1) attenuates the cardiac remodeling after MI.
[Methods] Anterior MI was produced in male mice by ligating the left anterior descending coronary artery (control group). In the MR16–1 group, intraperitoneal injection of MR16–1 (500 μg/body) was performed after coronary ligation. After 3 days, myocardial myeloperoxidase (MPO) activity was measured spectrophotometrically, and myocardial MCP-1 content was measured by ELISA. Myocardial infarct size and myocyte apoptosis were examined by histological analysis. After 1 week, myocardial matrix metalloproteinase 2 (MMP-2) activity was examined by gelatin zymography. After 4 weeks, echocardiography was performed, and then cardiac tissue was collected for histological examination.
[Results] MR16–1 improved the survival rate of mice with MI at 4 weeks. Myocardial infarct size and myocyte apoptosis were similar between groups. Myocardial MPO activity and MCP-1 content in the non-infarct area did not changed in both groups compared with the sham-operated heart. In contrast, in the infarct area, MPO activity and MCP-1 content were increased 2-fold and 4-fold, respectively, compared with the sham-operated heart, while MR16–1 significantly attenuated these increases. In addition, myocardial MMP-2 activity was elevated in both non-infarct and infract areas3-fold and 6-fold, respectively, while MR16–1 significantly attenuated this elevation in both areas. Four weeks after MI, MR16–1 significantly improved fractional shortening (MR16–1 group: 21.5±2.9% vs. control group: 12.8±1.9%, p<0.05) and reduced LV end-diastolic diameter (MR16–1 group: 4.1±0.5 mm vs. control group: 5.0±0.1 mm, p<0.01). Histological analysis showed that MR16 –1 significantly decreased myocyte hypertrophy and myocardial fibrosis in the non-infarct area.
[Conclusion] Injection of MR16 –1 after MI suppressed myocardial inflammation, resulting in the attenuation of cardiac remodeling. Therapies designed to inhibit IL-6 signaling may be novel strategy to attenuate cardiac remodeling after MI.