title: Effects of simvastatin in abdominal sepsis in rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Program in Health Sciences, UFRN, Brazil.
authors.forename: José Luiz de
authors.initials: JL
authors.lastname: Souza Neto
authors.forename: Irami
authors.initials: I
authors.lastname: Araújo Filho
authors.forename: Amália Cínthia Meneses do
authors.initials: AC
authors.lastname: Rego
authors.forename: Víctor Almeida
authors.initials: VA
authors.lastname: Dominici
authors.forename: Italo Medeiros
authors.initials: IM
authors.lastname: Azevedo
authors.forename: Eryvaldo Sócrates Tabosa
authors.initials: ES
authors.lastname: Egito
authors.forename: José
authors.initials: J
authors.lastname: Brandão-Neto
authors.forename: Aldo Cunha
authors.initials: AC
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002432:Cecum / Q000601:surgery; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects; D008214:Lymphocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D019821:Simvastatin / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin