Conclusive data on intestinal ischemia and reperfusion pathophysiology have been obtained from experimental animal studies. Cytokine activity of TNFa, IL-6 and IL-8 have been associated with the inflammatory reaction following IR. As a prototypic member of the TNF-family, TNF-a is a key mediator of acute inflammation of which expression is readily induced following ischemia reperfusion of the small intestine. Interestingly, we did not detect an increase in TNFa message in our experiments. Similarly, IL-6 was demonstrated as an important component of the acute phase reaction, able to induce tissue injury and inflammation following mesenteric ischemia and reperfusion in IL-6 knockout mice. IL-6 controls endothelial cell injury, mediating successive neutrophil influx. Similarly, the chemokine IL-8 is involved in intestinal ischemia reperfusion induced inflammation. Administration of an inhibitory anti IL-8 antibody over the course of mesenteric IR in rats prevented neutrophil infiltration and protected the small intestine from IR injury. In keeping with these data, Il-6, IL-8 and TNFa gene expression did not increase in the absence of apoptotic cells, which were shed into the intestinal lumen immediately upon reperfusion. E-Selectin has an important role in the recruitment of leukocytes to sites of tissue injury. Its expression by vascular endothelial cells in response to injury is readily induced by cytokines IL-1 and TNFa. Interestingly, our data suggest that despite initial presence of damaged epithelial cells in response to an IR period, the rapid shedding of damaged epithelial Ingenol Mebutate debris largely averts endothelial cell activation. Consistent with this observation, PMN infiltration, assessed by total MPO tissue levels or the presence of HNP1-3 positive cells, in IR was not detected in our experiments. MPO, most abundantly released upon PMN Chloramphenicol activation, has been demonstrated to have a clear effect on the development of IR induced organ damage. Renal IR studies have demonstrated that MPO itself is able to contribute to the development of organ damage.