Effects of simvastatin in abdominal sepsis in rats

Statins are widely recognized as hypolipemic drugs, but some studies have observed anti-inflammatory and immunomodulatory effects, known as pleiotropic. The aims of this work was to study possible anti-inflammatory effects of simvastatin in abdominal sepsis. Serum pro-inflammatory cytokines and leukocytes count were determined in an experimental model of abdominal sepsis, using cecal ligation and puncture (CLP) in rats.

Twenty eight Wistar rats weighing 285+/-12 g were randomly divided in: CLP/Sinvastatin rats (n=7), treated with 10 mg/Kg of oral simvastatin 18 and 2 hs before CLP; CLP/Saline group rats (n=7), treated with oral saline; group Sham/Simvastatin (n=7), treated with simvastatin, and group Sham/Saline (n=7), treated with saline. Serum TNF-alpha, IL-1beta and IL-6 by ELISA and total leukocytes, neutrophils, lymphocytes, and eosinophils were determined 24 hs after CLP. ANOVA and Tukey test were used considering significant p<0.05.

It was demonstrated that serum TNF-alpha, IL-1beta and IL-6 were respectively 364.8+/-42 pg/mL; 46.3+/-18 pg/mL and 28.4+/-13 pg/mL in CLP/Sinvastatin rats, significantly lower (p<0.05) than in group CLP/Saline (778.5+/-86 pg/ml; 176.9+/-46 pg/ml; 133.6+/-21 pg/ml, respectively). The same results were observed in total leukocytes and neutrophils counts.

These results clearly demonstrate that simvastatin is an effective agent that reduces cytokines levels and leukocyte count in sepsis, independently of its well-known lipid-lowering effects. Thus, HMG-CoA reductase inhibitors like simvastatin have important anti-inflammatory effects in abdominal sepsis in rats.