| Summary: | 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. === Surgery, Department of === Medicine, Faculty of === Graduate
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