Decreased death receptor pathway of apoptotic signaling in the septic mouse gut: effect of nutritional support

Background: Sepsis is a systemic inflammatory response syndrome (SIRS) caused by infection. Sepsis remains a cause of death in patients in intensive care. In sepsis, death receptors such as tumor necrosis factor receptor 1 (TNF-R1), Fas, and caspase-3 are related to sepsis-induced apoptosis. Conversely, the nutritional support including enteral nutrition (EN) is considered an effective therapy in the intensive care unit. In the digestive tract, the detailed mechanisms of these death receptors and caspase-3 remain unknown in septic status. Methods: We examined the expression of TNF-R1, Fas, and activated caspase-3 and compared the effect of nutritional support with EN in the digestive tract of septic mice. Polymicrobial sepsis was induced by cecal ligation and puncture(CLP) in CD1/ICR mice. We investigated TNF-R1, Fas, and caspase-3 activation in the mouse digestive tract and compared different feed therapies including EN. Result: In this study, we observed that the expression of TNF-R1, Fas, and cleaved caspase-3 was elevated in the duodenum, jejunum, and ileum of CLP-induced septic mice. In the ileum of CLP-induced septic mice with EN, the expression of death receptors (TNF-R1 and Fas) and cleaved caspase-3 was downregulated. Conclusions: In the digestive tract, our results suggest that nutritional support including EN can be an effective therapy for sepsis-induced apoptosis.