Marked difference in tumor necrosis factor-alpha expression in warm ischemia- and cold ischemia-reperfusion of the rat liver

Although tumor necrosis factor-alpha has been implicated in liver injury af ter both warm ischemia- and cold ischemia-reperfusion, it is unclear whethe r reactivity of the liver to these stimuli is similar with regard to cytoki ne expression. Hers we compare the effects of warm and cold ischemia on tum or necrosis factor-alpha expression and test the hypothesis that cold ische mia preceding warm ischemia causes overexpression of this cytokine. Rat liv ers were hushed out with University of Wisconsin solution and subjected to varying periods of warm ischemia. cold ischemia, or cold ischemia plus warm ischemia followed by reperfusion using a blood-free perfusion model. Tumor necrosis factor-alpha and interleukin-10 release into the perfusate and bi le were measured by ELISA, and expression of these cytokines and that of c- fos, c-jun. and c-myc were studied by reverse-transcriptase polymerase chai n reaction. We found high levels of tumor necrosis factor-alpha in the perf usates of livers subjected to warm ischemia-reperfusion. whereas minimal or no tumor necrosis factor-alpha was detected in livers subjected to cold is chemia-reperfusion or to cold ischemia plus warm ischemia-reperfusion. Reve rse-transcriptase polymerase chain reaction confirmed the above findings an d showed that immediate early genes were expressed in reperfused groups of liver. Measurements of cytokine release into bile showed that neither tumor necrosis factor-alpha nor interleukin-10 were upregulated hy cold ischemia -reperfusion. The results suggest that (1) warm ischemia- and cold ischemia -reperfusion of rat liver lead to very different outcomes with regard to tu mor necrosis factor-alpha expression and (2) cold ischemia preceding warm i schemia prevents upregulation of tumor necrosis factor-alpha. (C) 2000 Acad emic Press.