Atorvastatin enhances interleukin-10 levels and improves cardiac function in rats after acute myocardial infarction

Christian Stumpf (1) , Sebastian Petzi , Katrin Seybold , Gerald Wasmeier , Martin Arnold , Dorette Raaz , Atilla Yilmaz , Werner G. Daniel , Christoph D. Garlichs

1 Medical Clinic II - Cardiology

Left ventricular (LV) remodeling is the basic mechanism of heart failure (HF) following myocardial infarction (MI). Whereas there is evidence that pro-inflammatory cytokines (including TNF-α and IL-6) are involved in the remodeling process, only little is known about the role of anti-inflammatory cytokines, such as IL-10. Since accumulating evidence revealed that statins possess anti-inflammatory properties, the goal 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 left anterior descending (LAD) branch ligation, were treated for 4 weeks with atorvastatin (10 mg/kg/d via oral gavage) starting on the first day after MI induction. Cardiac function was assessed by echocardiography and cardiac catheterization 4 weeks after MI induction. Membrane-bound and soluble fractions of TNF-α, IL-6 and IL-10 protein, the ratio of TNF-α to IL-10, serum levels of MCP-1 as well as myocardial macrophage infiltration were analyzed. Treatment with atorvastatin significantly improved post MI LV function (FS + 120%;, dP/dt max} +147%; LVEDP -27%). Furthermore atorvastatin treatment markedly decreased levels of TNF-α, 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 shifting the balance between pro-inflammatory and anti-inflammatory cytokines towards the anti-inflammatory direction, as given in a significantly decreased TNF-α to IL-10 ratio. Atorvastatin ameliorated early LV remodeling and improved LV function in rats with heart failure 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, of how atorvastatin influences post-MI remodeling and thus improves LV function.

Mots clés: Medicine

Christian Stumpf, Sebastian Petzi, Katrin Seybold, Gerald Wasmeier, Martin Arnold, et al.. Atorvastatin enhances interleukin-10 levels and improves cardiac function in rats after acute myocardial infarction. Clinical Science, 2008, 116 (1), pp.45-52. ⟨10.1042/CS20080042⟩. ⟨hal-00479426⟩