Enteral Feeding Decreases Gut Apoptosis, Permeability, And Lung Inflammation During Murine Endotoxemia

Kurt T. Alscher, P. Terry Phang, Treena E. McDonald, Keith R. Walley

Save to my Library

Download PDF

We tested the hypothesis that endotoxemia and fasting are associated with increased gut apoptotic activity, gut permeability, and inflammation in a distant organ. Fed or fasted CD-1 mice were studied 6 h after intraperitoneal injection of either saline (sham) or endotoxin (4 mg/kg of 0111:B4 Escherichia coli lipopolysaccharide). We found that endotoxin increased gut caspase-3 and -6 activity by 4.9 ± 0.6- and 4.5 ± 0.5-fold, respectively ( P < 0.001), and increased terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) staining of mucosal cells ( P< 0.05). Feeding decreased caspase-3 activity by 40% ( P< 0.05) and decreased endotoxin-induced TUNEL staining ( P< 0.05). Endotoxin increased gut poly(ADP-ribose) polymerase activity by 15% ( P < 0.05). Endotoxin increased gut permeability by 44% ( P < 0.05), an effect reduced 36% by feeding ( P < 0.05). Similarly, endotoxin increased pulmonary neutrophil infiltration (6.0 ± 1.0-fold, P< 0.001) and increased lung interleukin (IL)-6 (5.9 ± 0.1-fold, P < 0.001) and macrophage inflammatory protein (MIP)-2 expression (290 ± 40-fold, P < 0.001), whereas feeding decreased this effect by 43% for neutrophils, 40% for IL-6 ( P < 0.05), and 35% for MIP-2 ( P < 0.05). Thus endotoxin increases gut apoptotic activity, gut permeability, and pulmonary inflammation. Enteral feeding may decrease the distant organ inflammation by reducing gut apoptosis, thereby maintaining gut mucosal function during endotoxemia.