Role of reactive oxygen intermediates in interleukin 10 release after cold liver ischemia and reperfusion in mice.
OBJECTIVE
Reactive oxygen intermediates and cytokines are key effectors 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 reperfusion of cold-preserved livers.


METHODS
An endotoxin-free isolated perfused mouse liver system was designed. Harvested mouse livers were stored at 4 degrees C for 0-28 hours and reperfused for 90 minutes with a warm oxygenated Hank's balanced salt solution (alone or with additives). Cytokine messenger RNA (mRNA) from whole liver was measured by reverse-transcription polymerase chain reaction. Cytokine protein levels and liver injury assessed by alanine aminotransferase levels were evaluated in liver effluent during reperfusion.


RESULTS
TNF and IL-10 mRNA and protein concentrations were increased after reperfusion of ischemic 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-kappaB mobilization (-73% and -76% for TNF and IL-10, respectively). Liver injury was decreased 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.
Le Moine
O
O
Department of Gastroenterology, Hôpital Erasme, Brussels, Belgium.
Louis
H
H
Stordeur
P
P
Collet
J M
JM
Goldman
M
M
Devière
J
J
D000818:Animals; D003080:Cold Temperature; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D007511:Ischemia / Q000378:metabolism*; D008099:Liver / Q000098:blood supply*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10