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Enteral feeding decreases gut apoptosis, gut permeability, and pulmonary inflammation during murine endotoxemia Alscher, Kurt Thomas


Background: The systemic response to sepsis is associated with gut mucosal damage, increased permeability, and subsequently increased inflammation in distant organs. Enteral feeding may reduce mortality from multiple organ failure by maintaining the gut mucosal barrier, however the mechanism of this is unclear. We tested the hypothesis that endotoxemia is associated with increased gut apoptosis, increased gut permeability, and increased pulmonary inflammation. Furthermore, we postulate that enteral feeding ameliorates endotoxin's effect on these parameters. Methods: Four groups of 10 male CD-1 mice were studied: fed/sham, fasted/sham, fed/endotoxemic, fasted/endotoxemic. Fasted mice were denied food for 16 hours prior to injection of either saline or E. coli endotoxin. Fed animals received rodent chow throughout. Six hours post injection the gut and lungs were removed and frozen. We assessed gut apoptosis by measuring gut caspase 3, caspase 6 and PARP enzymatic activity. Gut permeability was quantified by measuring the transfer of fluorescein labeled dextran (FD-4) across the gut wall, and pulmonary inflammation was quantified by lung interleukin 6 (IL-6) and macrophage inflammatory protein-2 (MIP-2) ELISA. Results: 1) Apoptosis - After LPS injection, gut caspase 3 and 6 activity increased by 4.9 fold and 4.5 fold respectively (p<0.001); fed mice given endotoxin had 40% less caspase 3 activity and 20% less caspase 6 activity than fasted mice given endotoxin. Gut PARP activity was 15% higher in endotoxemic mice than controls (p<0.05) 2) Gut permeability - Endotoxemic mice had 44% (p<0.05) more FD-4 present in their serum than the sham mice; fed mice given endotoxin had 36% (p<0.05) less FD-4 than the fasted animals given endotoxin. 3) Pulmonary inflammation - After LPS injection, pulmonary IL-6 increased by 7.4 fold (p<0.001); fed animals had 40% less IL-6 than the fasted (p<0.05) mice given endotoxin. Lung MIP-2 increased by 292.1 fold (p<0.001) after LPS injection; fed animals had 35% less MIP-2 than their fasted counterparts within the endotoxemic group (p<0.05). Conclusions: Gut apoptosis, gut permeability, and pulmonary inflammation are increased during endotoxemia. Enteral feeding decreases gut apoptosis, and this is associated with improved gut barrier function and decreased pulmonary inflammation. Enteral feeding may decrease the systemic inflammatory response by maintaining gut mucosal function during endotoxemia.

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