Overexpression of Bcl-2 in the intestinal epithelium improves survival in septic mice

Craig M. Coopersmith, Katherine C. Chang, Paul E. Swanson, Kevin W. Tinsley, Paul E. Stromberg, Timothy G. Buchman, Irene E. Karl, Richard S. Hotchkiss

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

Objectives: 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. Design: Prospective, randomized, controlled trial. Setting: Animal laboratory in an academic medical center. Interventions: 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. Measurements and Main 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.

Original languageEnglish
Pages (from-to)195-201
Number of pages7
JournalCritical care medicine
Volume30
Issue number1
DOIs
StatePublished - 2002

Keywords

  • Apoptosis
  • Bcl-2
  • Caspase
  • Intestine
  • Lymphocyte
  • Mortality
  • Multiple organ failure
  • Necrosis
  • Programmed cell death
  • Septic shock

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