Overexpression of Bcl-2 in the intestinal epithelium improves survival in septic mice.
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.
Coopersmith
Craig M
CM
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA. coopersmithc@msnotes.wustl.edu
Chang
Katherine C
KC
Swanson
Paul E
PE
Tinsley
Kevin W
KW
Stromberg
Paul E
PE
Buchman
Timothy G
TG
Karl
Irene E
IE
Hotchkiss
Richard S
RS
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