EXPERIMENTAL STUDY
Neutralization of interleukin-1ß in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling
Myung-Woo Hwang, MD, PhDa,
Akira Matsumori, MD, PhD*,a,
Yutaka Furukawa, MD, PhDa,
Koh Ono, MD, PhDa,
Masaharu Okada, MD, PhDa,
Atsushi Iwasaki, MD, PhDa,
Masatake Hara, MD, PhDa,
Tadashi Miyamoto, MD, PhDa,
Masanao Touma, MDa and
Shigetake Sasayama, MD, PhDa
a Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
Manuscript received February 23, 2001;
revised manuscript received July 10, 2001,
accepted July 19, 2001.
* Reprint requests and correspondence: Dr. Akira Matsumori, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8397, Japan
amat{at}kuhp.kyoto-u.ac.jp
OBJECTIVES
We sought to examine the role of the pro-inflammatory cytokine, interleukin-1-beta (IL-1ß), 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-1ß was examined. In a second set of experiments, the mice underwent coronary artery ligation followed by treatment with anti–IL-1ß 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-1ß 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-1ß-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-1ß-treated mice.
CONCLUSIONS
Anti–IL-1ß 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-1ß appears to play a protective role.
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Abbreviations and Acronyms
| | IgG | = immunoglobulin G | | IL-1ß | = interleukin-1-beta | | LV | = left ventricular | | LVEDD | = left ventricular end-diastolic dimension | | MI | = myocardial infarction | | PBS | = phosphate-buffered saline | | PCR | = polymerase chain reaction | | RNA | = ribonucleic acid | | RT | = reverse transcription | TNF- | = tumor necrosis factor-alpha | | TTE | = transthoracic echocardiography |
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