title: Overexpression of Bcl-2 in the intestinal epithelium improves survival in septic mice.
abstract: OBJECTIVE
  The aim of this study was to determine whether decreasing intestinal epithelial apoptosis in sepsis would alter mortality rates. The roles of the antiapoptotic protein Bcl-2 and the "executioner" protease caspase-3 in sepsis-induced gut cell death also were evaluated.
  
  
  METHODS
  Prospective, randomized, controlled trial.
  
  
  METHODS
  Animal laboratory in an academic medical center.
  
  
  METHODS
  Transgenic mice that overexpress Bcl-2 throughout the small intestinal epithelium (n = 23) and littermate controls (n = 27) were subjected to cecal ligation and puncture (CLP) and followed for 8 days to assess survival. A second group of transgenic (n = 15) and littermate animals (n = 15) were subjected to CLP and were killed between 16 and 48 hrs postoperatively to assess for intestinal apoptosis and active caspase-3 staining.
  
  
  RESULTS
  Survival of transgenic animals was 83% 8 days after CLP compared with 44% for littermate controls (p < .005). Survival curves between the two groups of animals began diverging within 24 hrs. Overexpression of Bcl-2 was associated with a significant decrease in apoptosis between 16 and 24 hrs post-CLP (p < .05) as well as decreased staining for active caspase-3.
  
  
  CONCLUSIONS
  Decreasing intestinal epithelial cell death via overexpression of Bcl-2 improves survival in septic mice. The gut may play a central role in the pathophysiology of sepsis.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA. coopersmithc@msnotes.wustl.edu
authors.forename: Craig M
authors.initials: CM
authors.lastname: Coopersmith
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Chang
authors.forename: Paul E
authors.initials: PE
authors.lastname: Swanson
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Tinsley
authors.forename: Paul E
authors.initials: PE
authors.lastname: Stromberg
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Buchman
authors.forename: Irene E
authors.initials: IE
authors.lastname: Karl
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hotchkiss
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004848:Epithelium / Q000473:pathology; D019254:Genes, bcl-2 / Q000235:genetics*; D007413:Intestinal Mucosa / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D011446:Prospective Studies; D011897:Random Allocation