Damage to the intestinal mucosal barrier sustained during the compensated stages of shock may result in bacterial translocation and systemic accumulation of toxins, leading to sepsis and multiple organ failure. Neutrophils are known to be an important component of endotoxin and cytokine-induced tissue injury. The purpose of this study, therefore, was to test the hypothesis that neutrophil infiltration and MPO production accompany endotoxin and TNF induced intestinal mucosal dysfunction.
To evaluate mucosal dysfunction, jejunal blood-to-lumen clearances of chromium 51-labeled ethylenediaminetetraacetate (51Cr-EDTA) were measured in cats administered fetal calf serum (controls), endotoxin, TNF, or polyclonal anti-TNF antibody followed by endotoxin. Neutrophil accumulation in the jejunal mucosa was evaluated by histologic enumeration and measurement of jejunal myeloperoxidase (MPO) activity.
Endotoxin and TNF induced mucosal dysfunction in the proximal jejunum is accompanied by neutrophil accumulation in the jejunal mucosa as indicated by histologic enumeration and increased MPO activity. Pretreatment with anti-TNF polyclonal antibody significantly decreased endotoxin-induced increases in jejunal MPO activity. The results of this study support the contribution of neutrophils to endotoxin and TNF induced mucosal dysfunction.