title: The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical trial.
abstract: OBJECTIVE
  To determine if statin therapy reduces the incidence of severe sepsis and the levels of inflammatory cytokines in patients with acute bacterial infection.
  
  
  METHODS
  Double-blind placebo controlled randomized clinical trial.
  
  
  METHODS
  Department of medicine and medical intensive care unit in a tertiary university medical center.
  
  
  METHODS
  A total of 83 patients with suspected or documented bacterial infection were enrolled. We randomly assigned 42 patients to receive 40 mg of simvastatin orally, followed by 20 mg of simvastatin, and 41 to receive matching placebo.
  
  
  RESULTS
  The study was prematurely terminated due to slow recruitment rate. Here we report the analysis of the secondary outcome: change in cytokines levels at 72 h. Both groups were evenly matched in terms of co-morbidity and severity of illness on admission. Four of the 83 patients enrolled developed severe sepsis, two in each group. No difference was observed in other clinical variables and there were no mortalities. Cytokine levels were randomly assessed in 40 patients (20 in each group). Both TNF-alpha and IL-6 levels were significantly reduced in the simvastatin group (p = 0.02 and p = 0.02, respectively), while no such difference was observed in the placebo group (p = 0.35 and 0.39, respectively).
  
  
  CONCLUSIONS
  Statin therapy may be associated with a reduction in the levels of inflammatory cytokines in patients with acute bacterial infections. Large controlled trials will determine if this reduction will translate into a clinical benefit.
authors.affiliation: Department of Medicine, Faculty of Health Sciences, Soroka University Medical Center, Ben Gurion University of the Negev, Beersheba, Israel.
authors.forename: Victor
authors.initials: V
authors.lastname: Novack
authors.forename: Miruna
authors.initials: M
authors.lastname: Eisinger
authors.forename: Amit
authors.initials: A
authors.lastname: Frenkel
authors.forename: Marius
authors.initials: M
authors.lastname: Terblanche
authors.forename: Neill K J
authors.initials: NK
authors.lastname: Adhikari
authors.forename: Amos
authors.initials: A
authors.lastname: Douvdevani
authors.forename: Doron
authors.initials: D
authors.lastname: Amichay
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Almog
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001424:Bacterial Infections / Q000188:drug therapy*; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects* / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000517:prevention & control; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D019821:Simvastatin