The potential etiologic role of tumor necrosis factor in mediating multiple organ dysfunction in rats following intestinal ischemia-reperfusion injury.

Endogenous inflammatory cytokines may function as mediators in the development of remote organ damage in response to local ischemic insult. This study was designed to (a) explore the potential role of tumor necrosis factor (TNF) formation in the pathogenesis of systemic tissue injury, (b) determine the relationship between induction of TNF and gut-derived endotoxemia and/or bacterial translocation, and (c) evaluate the protective effect of anti-TNF monoclonal antibody (MoAb) for vital organs following intestinal ischemia-reperfusion in rats. Animals were subjected to superior mesenteric artery occlusion (SMAO) for 45 min. Systemic plasma TNF levels increased rapidly after the onset of reperfusion, reaching a peak value 2 h later (P < 0.01). TNF elevation was found to be associated with gut origin endotoxemia, where the maximal TNF levels occurred approximately 2 h after the initial appearance of endotoxin in portal vein. Prophylactic treatment with anti-TNF MoAb markedly blunted the elevation in plasma TNF levels and afforded protection from the development of hypotension, vital organs dysfunction, and metabolic acidosis. Significant improvement in 48-h survival rate was observed by administration of anti-TNF MoAb prior to inducing ischemia (P = 0.007). These findings suggest that intestinal ischemia-reperfusion could result in TNF production, which may play a key role in mediating subsequent septic response and systemic tissue injury. It seems likely that passage of endotoxin and bacteria from the gut can be responsible for the TNF formation