O. Lemoine et al., ROLE OF REACTIVE OXYGEN INTERMEDIATES IN INTERLEUKIN-10 RELEASE AFTERCOLD LIVER ISCHEMIA AND REPERFUSION IN MICE, Gastroenterology, 113(5), 1997, pp. 1701-1706
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.