Neutralization of interleukin-1 beta in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling

OBJECTIVES We sought to examine the role of the pro-inflammatory cytokine, interleukin-1-beta (IL-1 beta), in the process of left ventricular (LV) rem odeling in the early phase after myocardial infarction (MI). BACKGROUND Studies have shown that pro-inflammatory, cytokines are closely related to the progression of LV remodeling after MI. METHODS Mice underwent coronary artery ligation, and the time course of LV remodeling was followed up to 20 weeks. The gene expression level of IL-1 b eta was examined. In a second set of experiments, the mice underwent corona ry artery ligation followed by treatment with anti-IL-1 beta antibody (100 mug, intravenously), versus control immunoglobulin G (100 mug, intravenousl y) immediately after the operation. RESULTS Rapid hypertrophy of noninfarcted myocardium was observed by four w eeks, and interstitial fibrosis progressed steadily up to 20 weeks. Anti-IL -1 beta treatment increased the occurrence of ventricular rupture and suppr essed collagen accumulation in the infarct-related area. At four and eight weeks after the operation, total heart weight and LV end-diastolic dimensio n were significantly greater in the anti-IL-1 beta -treated mice than in th e other groups. In the infarct-related area, collagen accumulation was supp ressed, whereas in the noninfarcted area, pro-collagen gene expression leve ls, particularly, type III, were decreased in the anti-IL-1 beta -treated m ice. CONCLUSIONS Anti-IL-1 beta treatment suppressed pro-collagen gene expressio n and delayed wound healing mechanisms-properties that are likely to lead t o progression of LV remodeling. In the acute phase of MI, IL-1 beta appears to play, a protective role. (J Am Coll Cardiol 2001;38:1546-53) (C) 2001 b y the American College of Cardiology.