Effect of FR167653 on small bowel ischemia-reperfusion injury in dogs

IL-1 and TNF-alpha are known to be pleiotropic cytokines associated with va rious inflammatory conditions such as small intestinal injury after ischemi a-reperfusion. FR167653 has been characterized as a potent suppressant of I L-1 and TNF-alpha production. The effect of FR167653 on intestinal reperfus ion injury was investigated in a warm ischemia model of the canine gut. Six teen mongrel dogs were divided into two groups: a control group and a FR gr oup to which FR167653 was administered. Both the superior mesenteric artery and vein were clamped for 2 hr. Arterial pH, hepatic venous hemoglobin oxy gen saturation, intramucosal pH, and the survival rate were well maintained in the FR group in comparison with the control group after reperfusion. FR 167653 inhibited the expression of IL-1 beta mRNA. Histologically, ischemia -reperfusion injury was more severe in the control group than the FR group. This study suggests that FR167653 inhibits proinflammatory cytokines and a meliorates ischemia-reperfusion injury of the small intestine.