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Significance of changes in TNF- and IL-10 levels in the progression of heart failure subsequent to myocardial infarction

Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Center, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

Submitted 16 December 2005 ; accepted in final form 27 January 2006

We tested whether a decrease in the ratio of interleukin-10 (IL-10) to tumor necrosis factor- (TNF-) correlates with the decrease in cardiac function in heart failure. It has been suggested that TNF- plays a role in the progression of heart failure, and the effect of TNF- in many tissues is modulated by IL-10. Any relation of these two cytokines to heart failure has never been examined. Cardiac function was assessed by echocardiographic and hemodynamic techniques in coronary artery-ligated rats at 1, 4, 8, and 16 wk after myocardial infarction (MI). Membrane-bound and soluble fractions of TNF- and IL-10 proteins, the ratio of TNF- to IL-10, and TNF- and IL-10 mRNA levels were analyzed. Losartan was used to modify cardiac function in rats 4 wk after MI to further validate the relation between the IL-10-to-TNF- ratio and cardiac function. Cardiac function deteriorated with time in all coronary artery-ligated groups, with severe failure at 16 wk after MI. Membrane-bound and soluble TNF- protein fractions were increased 1 and 4 wk after MI, whereas TNF- mRNA was increased 4 and 8 wk after MI. Membrane-bound IL-10 protein and mRNA levels were decreased 4, 8, and 16 wk after MI. The decrease in the IL-10-to-TNF- protein ratio in all coronary artery-ligated groups correlated with the depressed cardiac function. Losartan improved cardiac function, membrane-bound and soluble TNF- and IL-10 protein levels, the ratio of IL-10 to TNF-, and IL-10 mRNA. This study suggests that a decrease in IL-10 and IL-10-to-TNF- ratio correlates with depressed cardiac function.

cardiac function; cytokines; congestive heart failure

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