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

• Published in: Journal of the American College of Cardiology 2001-11, Vol.38 (5), p.1546-1553
• Main Authors: Hwang, Myung-Woo, Matsumori, Akira, Furukawa, Yutaka, Ono, Koh, Okada, Masaharu, Iwasaki, Atsushi, Hara, Masatake, Miyamoto, Tadashi, Touma, Masanao, Sasayama, Shigetake
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cardiology. Vascular system; Coronary heart disease; Heart; Medical sciences
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(01)01591-1

OBJECTIVES We sought to examine the role of the pro-inflammatory cytokine, interleukin-1-beta (IL-1β), in the process of left ventricular (LV) remodeling 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-1β was examined. In a second set of experiments, the mice underwent coronary artery ligation followed by treatment with anti–IL-1β antibody (100 μg, intravenously), versus control immunoglobulin G (100 μg, intravenously) immediately after the operation. RESULTS Rapid hypertrophy of noninfarcted myocardium was observed by four weeks, and interstitial fibrosis progressed steadily up to 20 weeks. Anti–IL-1β treatment increased the occurrence of ventricular rupture and suppressed collagen accumulation in the infarct-related area. At four and eight weeks after the operation, total heart weight and LV end-diastolic dimension were significantly greater in the anti–IL-1β-treated mice than in the other groups. In the infarct-related area, collagen accumulation was suppressed, whereas in the noninfarcted area, pro-collagen gene expression levels, particularly type III, were decreased in the anti–IL-1β-treated mice. CONCLUSIONS Anti–IL-1β treatment suppressed pro-collagen gene expression and delayed wound healing mechanisms—properties that are likely to lead to progression of LV remodeling. In the acute phase of MI, IL-1β appears to play a protective role.