Expression and Role of Inflammatory Cytokines in Acute Myocardial Infarction -usingTNF, IL-1, Il-6 knock out mice-

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1. Acute myocardial infarction model was made by ligation of left anterior descending coronary arteries of TNF-α knock out mice (KO) and wild type (WT) mice. At 1, 3 and 7 days after infarction, cardiac ultrasound was performed, and the heart was excised for histological. immunohistochemical and morphological analysis.2. Tissue levels of TNF-α and IL-6were increased in infarcted and non-infarcted areas in WT at 1 day after infarction and increased more at 3 days.3. In ultrasound study, end-diastolic diameter was smaller in KO than in WT, and fractional shortening was higher in KO than WT at 3 and 7 days after infarction. Infiltration of inflammatory cells was observed from 1 day, and infiltration of macrophages were prominent at 3 days in histological examination, those of which were less in KO than WT in any period. Myocardial necrosis was prominent at 3 days, and wall thinning and left ventricular enlargement were observed at 7 days. In immnunohistochemical analysis, expression of metalloproteinase 2, 9, 13 was observed in infiltrating cells and cardiomyocytes in infracted and peri-infarcted areas at 1 day and prominent at 3 and 7 days. Those expressions were less in KO than in WT in any period. Furthermore, TUNEL positive cells representing apoptotic cells were less in KO than in WT in peri-infarcted area.4. In KO mice, the degree of myocardial damage was less marked, and the expression of metalloproteinase was smaller than in WT, suggesting the involvement of TNF-α in the pathogenesis after myocardial infarction partly through metalloproteinase. The expression of metalloproteinase in non-infarcted area indicates the involvement of metalloproteinase in the cardiac remodeling. Anti-cylokine therapy on cardiac failure and remodeling may became a useful strategy.