Significance of changes in TNF-alpha and IL-10 levels in the progression of heart failure subsequent to myocardial infarction.
We tested whether a decrease in the ratio of interleukin-10 (IL-10) to tumor necrosis factor-alpha (TNF-alpha) correlates with the decrease in cardiac function in heart failure. It has been suggested that TNF-alpha plays a role in the progression of heart failure, and the effect of TNF-alpha 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-alpha and IL-10 proteins, the ratio of TNF-alpha to IL-10, and TNF-alpha 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-alpha 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-alpha protein fractions were increased 1 and 4 wk after MI, whereas TNF-alpha 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-alpha protein ratio in all coronary artery-ligated groups correlated with the depressed cardiac function. Losartan improved cardiac function, membrane-bound and soluble TNF-alpha and IL-10 protein levels, the ratio of IL-10 to TNF-alpha, and IL-10 mRNA. This study suggests that a decrease in IL-10 and IL-10-to-TNF-alpha ratio correlates with depressed cardiac function.
Kaur
K
K
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Center, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada R2H 2A6.
Sharma
A K
AK
Singal
P K
PK
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10