title: Inhibition of intestinal epithelial apoptosis and survival in a murine model of pneumonia-induced sepsis.
abstract: BACKGROUND
  Increased intestinal epithelial apoptosis is present in both human autopsy studies and animal models of sepsis. Whether altering gut apoptosis decreases mortality in sepsis induced by pathogenic bacteria outside the gut is unknown.
  
  
  OBJECTIVE
  To determine if decreasing levels of intestinal cell death improves survival in a murine model of Pseudomonas aeruginosa pneumonia-induced sepsis.
  
  
  METHODS
  Prospective study in which transgenic mice that overexpress the antiapoptotic protein Bcl-2 in their intestinal epithelium (n = 25) and control littermates (n = 26) were subjected to intratracheal injection of P aeruginosa.
  
  
  METHODS
  Survival at 7 postoperative days, compared between the 2 groups. Secondary outcomes included quantification of gut epithelial apoptosis.
  
  
  RESULTS
  Survival in transgenic mice that overexpress Bcl-2 in the intestinal epithelium was 40% (10/25) compared with 4% (1/26) in control littermates 7 days after intratracheal injection of P aeruginosa (P =.001), with differences in survival noted within 24 hours of surgery. Overexpression of Bcl-2 was associated with a decrease in gut epithelial apoptosis demonstrated by active caspase 3 staining, the terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay, and hematoxylin-eosin staining.
  
  
  CONCLUSIONS
  In this murine model, inhibiting gut epithelial apoptosis by overexpression of Bcl-2 was associated with a survival advantage in P aeruginosa pneumonia-induced sepsis. These results suggest that intestinal epithelial apoptosis may play a role in sepsis-related mortality.
authors.affiliation: Department of Surgery, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8109, St Louis, MO 63110, USA. coopersmithc@msnotes.wustl.edu
authors.forename: Craig M
authors.initials: CM
authors.lastname: Coopersmith
authors.forename: Paul E
authors.initials: PE
authors.lastname: Stromberg
authors.forename: W Michael
authors.initials: WM
authors.lastname: Dunne
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Davis
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Amiot
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; D018988:Bacterial Translocation; D053148:Caspase 3; D020169:Caspases; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019254:Genes, bcl-2; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018410:Pneumonia, Bacterial; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000503:physiopathology*; D018805:Sepsis / Q000503:physiopathology*; D016019:Survival Analysis
chemical_list: D016207:Cytokines; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases