Journal
CRITICAL CARE MEDICINE
Volume 30, Issue 1, Pages 195-201Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00003246-200201000-00028
Keywords
apoptosis; intestine; septic shock; multiple organ failure; Bcl-2; mortality; programmed cell death; lymphocyte; necrosis; caspase
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Funding
- NIGMS NIH HHS [GM55194, GM00709, GM44118] Funding Source: Medline
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R37GM044118, K08GM000709, R01GM055194, R01GM044118] Funding Source: NIH RePORTER
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Objectives: The aim of this study was to determine whether decreasing intestinal epithelial apoptosis in sepsis would after 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.
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