Interleukin-1 Trap Attenuates Cardiac Remodeling After Experimental Acute Myocardial Infarction in Mice

Background: Interleukin-1 (IL-1) is an inflammatory cytokine that responds as an acute phase reactant during acute myocardial infarction. Conflicting data describe the role of anti-IL-1 interventions to reduce cardiac remodeling after AMI. IL-1 Trap is a modified recombinant fusion protein that binds circulating IL-1. Our study evaluated the effects of murine IL-1 Trap on cardiac remodeling after AMI resulting from permanent surgical coronary artery ligation. Methods: Mice received treatment with intraperitoneal injection of murine IL-1 Trap (1 mg/kg [n = 5], 5 mg/kg [n = 5], or 30 mg/kg [n = 5]) or NaCl 0.9% (saline; n = 10) every 48 hours after surgery. Transthoracic echocardiography was performed at baseline and 7 days after surgery. Inhibition of IL-1 signaling was determined by measurement of IL-6 plasma levels (enzyme-linked immunosorbent assay) after IL-1 beta injection. Apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) was measured in murine heart samples and in a primary culture of murine cardiomyocytes. Results: Mice treated with 5 mg/kg or 30 mg/kg IL-1 Trap had more favorable cardiac remodeling and echocardiographic assessment of infarct size at 7 days compared with saline (P < 0.05 for each comparison). Treatment with IL-1 Trap also reduced apoptosis and IL-6 levels compared with saline treatment. Conclusions: IL-1 Trap ameliorates cardiac remodeling and reduces cardiomyocyte apoptosis after experimental acute myocardial infarction in the mouse.