Insulin-like growth factor-1 levels contribute to the development of bacterial translocation in sepsis.

Abstract

RATIONALE Many lines of evidence point toward the gastrointestinal (GI) tract in the pathophysiology of organ dysfunction in sepsis. Splanchnic hypoperfusion during sepsis leads to enterocyte apoptosis, diminished barrier function, and release of bacterial products. Sepsis lowers levels of insulin-like growth factor (IGF)-1, a known antiapoptotic factor. We recently demonstrated that treatment with IGF-1 is protective in murine sepsis. OBJECTIVES We hypothesize that decreased IGF-1 levels in sepsis contributes to the development of bacterial translocation. METHODS Sepsis was induced in C57BL/6 mice via intratracheal instillation of Pseudomonas aeruginosa. Human subjects with sepsis were enrolled if they had a documented positive blood culture with a nonenteric organism. Bacterial translocation was measured in serum by quantitative real-time polymerase chain reaction with primers specific for enteric bacteria. Serum IGF-1 was measured by ELISA. Apoptosis of the GI epithelium was assessed via immunohistochemistry. MEASUREMENTS AND MAIN RESULTS We found that mice with severe sepsis had evidence of bacterial translocation by 24 hours. Enteric bacterial load correlated inversely with levels of serum IGF-1. If we treated mice with IGF-1, bacterial translocation was significantly decreased. In addition, we found increased GI epithelial cell apoptosis after sepsis, which was significantly decreased after IGF-1 treatment. Human subjects with nonenteric sepsis developed progressive enteric bacteremia over 3 days. The degree of enteric bacteremia correlated inversely with serum IGF-1 levels. CONCLUSIONS These data support the hypothesis that sepsis-induced reductions in IGF-1 levels contribute to the development of bacterial translocation in both a murine model and human subjects.

DOI: 10.1164/rccm.200911-1757OC

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@article{Hunninghake2010InsulinlikeGF, title={Insulin-like growth factor-1 levels contribute to the development of bacterial translocation in sepsis.}, author={Gary W. Hunninghake and Kevin C. Doerschug and Amanda B. Nymon and Gregory A . Schmidt and David K. Meyerholz and Alix Ashare}, journal={American journal of respiratory and critical care medicine}, year={2010}, volume={182 4}, pages={517-25} }