ROLE OF REACTIVE OXYGEN INTERMEDIATES IN INTERLEUKIN-10 RELEASE AFTERCOLD LIVER ISCHEMIA AND REPERFUSION IN MICE

Background & Aims: Reactive oxygen intermediates and cytokines are key effecters in reperfusion injury after liver ischemia, We hypothesized that reactive oxygen intermediates act as a signal for the release of tumor necrosis factor (TNF) and interleukin 10 (IL-10) after reperfus ion of cold-preserved livers, Methods: An endotoxin-free isolated perf used mouse liver system was designed, Harvested mouse livers were stor ed at 4 degrees C for 0-28 hours and reperfused for 90 minutes with a warm oxygenated Rank's balanced salt solution (alone or with additives ), Cytokine messenger RNA (mRNA) from whole liver was measured by reve rse-transcription polymerase chain reaction, Cytokine protein levels a nd liver injury assessed by alanine aminotransferase levels were evalu ated in liver effluent during reperfusion, Results: TNF and IL-10 mRNA and protein concentrations were increased after reperfusion of ischem ic livers, N-Acetylcysteine and allopurinol dramatically decreased TNF (-64% and -62%) and IL-10 (-49% and -57%) levels in the effluents, as did an inhibitor of the transcription factor NF-kappa B mobilization (-73% and -76% for TNF and IL-10, respectively), Liver injury was decr eased by -40%, -43%, and -54% for the three inhibitors, respectively, Conclusions: Reactive oxygen intermediates are involved in TNF and IL- 10 release after reperfusion of cold-preserved livers.