Interleukin-10 improves left ventricular function in rats with heart failure subsequent to myocardial infarction.
Evidence has shown that pro-inflammatory cytokines, especially TNF-alpha, are involved in the inflammatory response in the remodelling process after myocardial infarction (MI). Although IL-10, an anti-inflammatory cytokine, has been shown to antagonize some of the deleterious effects of TNF-alpha, little is known about its role in post-MI left ventricular (LV) dysfunction. The aim of the present study was to investigate whether a therapy with rhIL-10 could be beneficial in an animal model of post-MI heart failure (HF). Rats with experimental MI were treated with rhIL-10 (75 microg/kg/d sc) starting directly after MI induction, and continuing for 4 weeks. Controls were untreated MI and sham-operated rats. Cardiac function was assessed by echocardiography and cardiac catheterization 4 weeks after MI induction. Membrane-bound and soluble fractions of TNF-alpha, IL-6 and IL-10, the ratio of TNF-alpha to IL-10, serum levels of MCP-1 as well as myocardial macrophage infiltration, were analyzed. Treatment with rhIL-10 significantly improved post-MI LV function (FS +127%;, dP/dt(max) +131%; LVEDP -36%). This effect was associated with a significant decrease in pro-inflammatory cytokine and chemokine levels (TNF-alpha, IL-6, MCP-1) and furthermore resulted in a reduced myocardial infiltration of macrophages.
Stumpf
Christian
C
Department of Cardiology, University of Erlangen-Nuremberg, Erlangen, Germany. ch.stumpf@web.de
Seybold
Katrin
K
Petzi
Sebastian
S
Wasmeier
Gerald
G
Raaz
Dorette
D
Yilmaz
Atilla
A
Anger
Thomas
T
Daniel
Werner G
WG
Garlichs
Christoph D
CD
D000818:Animals; D016207:Cytokines / Q000097:blood; D004452:Echocardiography; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D016753:Interleukin-10 / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects*
D016207:Cytokines; D011994:Recombinant Proteins; D016753:Interleukin-10