title: Statin (cerivastatin) protects mice against sepsis-related death via reduced proinflammatory cytokines and enhanced bacterial clearance.
abstract: BACKGROUND
  Death attributable to septic shock syndrome depends highly on the inflammatory response and cytokine production. Inhibition of inflammation is one of the many pleiotropic effects of statins. The aim of this study was to test the hypothesis that statins have a role in altering the host response to bacterial infections and thus would prove beneficial in the prevention of microbial sepsis.
  
  
  METHODS
  Male C57BL/6 and C3H/HeN mice received cerivastatin (4 mg/kg) or phosphate-buffered saline (PBS) intraperitoneally (i.p.), 24 and 1 h before and 24, 48, and 72 h after bacterial challenges. Sepsis was induced by i.p. injection of lipopolysaccharide (LPS) (45 mg/kg), Staphylococcus aureus (5 x 10(7) colony-forming units [CFU]/mouse), or Salmonella typhimurium (2.5 x 10(6) CFU/mouse).
  
  
  RESULTS
  Administration of cerivastatin improved significantly the survival rate of mice challenged with LPS (31% vs. 19% in the PBS group; p = 0.001), S. aureus (56% vs. 20% in PBS group; p = 0.01), or S. typhimurium (48% vs. 10% in PBS group; p = 0.03). Significantly reduced release of the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 was evident in cerivastatin-treated mice after LPS challenge. Cerivastatin-treated mice showed insignificant reductions in serum TNF-alpha and IL-6 concentrations after bacterial challenge. However, significantly accelerated bacterial clearance was demonstrated in cerivastatin-treated mice 24 h after S. typhimurium infection and 48 h after S. aureus infection.
  
  
  CONCLUSIONS
  Cerivastatin protects mice against LPS- and live bacteria-induced death, an effect associated with cerivastatin-attenuated pro-inflammatory cytokine production and enhanced bacterial clearance. Hence, application of statins in the clinical setting may prove beneficial in prevention of LPS or bacterial infection-related sepsis.
authors.affiliation: Department of Academic Surgery, University College Cork/National University of Ireland, Cork University Hospital, Cork, Ireland.
authors.forename: Mohammad Z
authors.initials: MZ
authors.lastname: Chaudhry
authors.forename: Jiang Huai
authors.initials: JH
authors.lastname: Wang
authors.forename: Siobhan
authors.initials: S
authors.lastname: Blankson
authors.forename: H Paul
authors.initials: HP
authors.lastname: Redmond
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000276:immunology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D011725:Pyridines / Q000494:pharmacology*; D012485:Salmonella typhi / Q000276:immunology; D012772:Shock, Septic / Q000276:immunology* / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C086276:cerivastatin