Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats

Abstract

Objective: The proinflammatory cytokines interleukin (IL)-1beta and IL-6 are supposed to be involved in various cardiovascular diseases including reperfusion injury and cardiac hypertrophy.

Methods and results: In the present study, we have examined the cytokine expression from 3 h up to 12 weeks after permanent coronary artery occlusion in rats. In the first 3-12 h, there was a strong induction in IL-1beta and IL-6 mRNA expression in the infarct area (up to 50-fold) as well as in the non-infarcted myocardium (up to 15-fold). From day 3 onwards the cytokine expression was not significantly altered compared to sham-operated controls. In addition, the expression of C/AATT-enhancer binding protein-beta was about fourfold elevated in the first hours after myocardial infarction, but not thereafter. Furthermore, the expression of gp130 and IL-6 receptor increased significantly in the infarct area. The elevation in cytokine expression preceded the increase in matrix-metalloproteinase-9 in the infarct area as well as the increase in ANP and collagen expression in the non-infarcted myocardium.

Conclusions: We suggest that IL-6 and IL-1beta act synergistically in promoting resorption of the necrotic tissue, matrix remodeling and wound healing. Furthermore, they may be involved in the early induction of fibrosis and compensatory cardiac hypertrophy of the non-infarcted myocardium, but seem not to play a key role in long-term cardiac remodeling in chronic heart failure after myocardial infarction.