GUT ISCHEMIA AND MESENTERIC SYNTHESIS OF INFLAMMATORY CYTOKINES AFTERHEMORRHAGIC OR ENDOTOXIC-SHOCK

The intestine plays a major role in the pathophysiology of multiorgan failure. Although the systemic inflammatory response might be induced by endotoxin released through bacterial translocation, other factors s uch as intestinal ischemia might be implicated. We investigated the re lationship between intestinal ischemia-reperfusion and cytokine releas e in rat models of hemorrhagic or endotoxic shock. Plasma levels of tu mor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), lactate, and endotoxin, as well as macrophage TNF-alpha and IL-6 mRNA expressio n, were assessed at the end of shock and resuscitation. Hemodynamic ch anges and lactate levels suggested the presence of intestinal ischemia in both models. Mesenteric levels of TNF-alpha and IL-6 were increase d by hemorrhage and further increased after saline resuscitation. Simi lar results were obtained with mRNA cytokine gene expression in macrop hages. Endotoxin was not detectable in the hemorrhagic group. Endotoxi c shock also increased production of cytokines, which, in contrast to hemorrhage, was not further increased by resuscitation. These results suggest that intestinal ischemia-reperfusion upon hemorrhage and resus citation may be a major trigger for cytokine gene expression in the ab sence of endotoxin.