PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: 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. METHODS: Twenty eight Wistar rats weighing 285+/-12 g were randomly divided in: CLP/Sinvastatinrats (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. RESULTS: 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/Sinvastatinrats, 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. CONCLUSION: 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.
Authors: Holger C Müller; Katharina Hellwig; Simone Rosseau; Thomas Tschernig; Andreas Schmiedl; Birgitt Gutbier; Bernd Schmeck; Stefan Hippenstiel; Harm Peters; Lars Morawietz; Norbert Suttorp; Martin Witzenrath Journal: Crit Care Date: 2010-07-30 Impact factor: 9.097