title: Atorvastatin enhances interleukin-10 levels and improves cardiac function in rats after acute myocardial infarction.
abstract: LV (left ventricular) remodelling is the basic mechanism of HF (heart failure) following MI (myocardial infarction). Although there is evidence that pro-inflammatory cytokines [including TNF-alpha (tumour necrosis factor-alpha) and IL-6 (interleukin-6)] are involved in the remodelling process, only little is known about the role of anti-inflammatory cytokines, such as IL-10. As accumulating evidence has revealed that statins possess anti-inflammatory properties, the aim of the present study was to elucidate the effect of atorvastatin on the modulation of the anti-inflammatory cytokine IL-10 and its effect on LV function in rats with HF subsequent to MI. Rats with MI, induced by permanent LAD (left anterior descending) branch coronary artery ligation, were treated for 4 weeks with atorvastatin (10 mg x kg(-1) of body weight x day(-1) via oral gavage) starting on the first day after induction of MI. 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 protein, the TNF-alpha/IL-10 ratio, serum levels of MCP-1 (monocyte chemoattractant protein-1) as well as myocardial macrophage infiltration were analysed. Treatment with atorvastatin significantly improved post-MI LV function (fractional shortening, +120%; dP/dt(max), +147%; and LV end-diastolic pressure, -27%). Furthermore atorvastatin treatment markedly decreased the levels of TNF-alpha, IL-6 and MCP-1, reduced myocardial infiltration of macrophages and significantly increased myocardial and serum levels of the anti-inflammatory cytokine IL-10. Thus the balance between pro-inflammatory and anti-inflammatory cytokines was shifted in the anti-inflammatory direction, as shown by a significantly decreased TNF-alpha/IL-10 ratio. Atorvastatin ameliorated early LV remodelling and improved LV function in rats with HF subsequent to MI. Our study suggests that the modulation of the balance between pro- and anti-inflammatory cytokines towards the anti-inflammatory cytokine IL-10 is one salutary mechanism underlying how atorvastatin influences post-MI remodelling and thus improves LV function.
authors.affiliation: Department of Cardiology, University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany. ch.stumpf@web.de
authors.forename: Christian
authors.initials: C
authors.lastname: Stumpf
authors.forename: Sebastian
authors.initials: S
authors.lastname: Petzi
authors.forename: Katrin
authors.initials: K
authors.lastname: Seybold
authors.forename: Gerald
authors.initials: G
authors.lastname: Wasmeier
authors.forename: Martin
authors.initials: M
authors.lastname: Arnold
authors.forename: Dorette
authors.initials: D
authors.lastname: Raaz
authors.forename: Atilla
authors.initials: A
authors.lastname: Yilmaz
authors.forename: Werner G
authors.initials: WG
authors.lastname: Daniel
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Garlichs
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006439:Hemodynamics / Q000187:drug effects; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D016753:Interleukin-10 / Q000097:blood*; D008264:Macrophages / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018487:Ventricular Dysfunction, Left / Q000097:blood; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D011758:Pyrroles; D016753:Interleukin-10; D000069059:Atorvastatin