Interleukin-6 Plays a Detrimental Role in LV Remodeling after an Acute Myocardial Infarction

Abstract

Introduction: Interleukin-6 (IL-6), a proinflammatory cytokine, has been implicated in various cardiovascular diseases, including myocardial ischemic injury. Although its expression has been shown to rise in the aftermath of an acute myocardial infarction (MI), its exact role in left ventricular (LV) remodeling and pathogenesis of ischemic cardiomyopathy remains unclear. Hypothesis: We hypothesized that the absence of IL-6 will have a favorable impact on LV remodeling after a reperfused MI. Methods: To simulate a human myocardial infarction, we used a model of reperfused MI because most MIs in humans are followed by spontaneous or interventional reperfusion. Age-matched male C57BL/6 control mice and IL-6 knockout (KO) mice were subjected to a 30-min occlusion of the LAD coronary artery followed by reperfusion. Cardiac structure and function were serially assessed by echocardiography at baseline (4 d before MI), at 48 h and 35 d after MI. Mice were sacrificed after 35 days for histological and biochemical assessments. Results: At 48 h post-MI, ejection fraction (EF) was similarly and significantly reduced in both groups compared with baseline, indicating that the ischemic injury was similar in both groups. However, 35 d after MI, IL-6 KO mice exhibited significantly greater EF compared with control mice (49.5 ± 2.2% in IL-6 KO mice vs 42.6 ± 1.3% in control mice). IL-6 KO mice had significantly smaller LV mass and cardiomyocyte size. Moreover, LV end-diastolic volume was significantly smaller in IL-6 KO mice, indicating superior remodeling. Conclusions: Genetic deletion of IL-6 ameliorates LV remodeling and systolic dysfunction after a reperfused myocardial infarction, indicating a deleterious role of IL-6 in LV remodeling after acute myocardial ischemia/reperfusion injury. Modulation of IL-6 signaling may therefore have therapeutic potential for patients after MI at risk for adverse remodeling and development of heart failure.