Effect of cold-ischemia time on nuclear factor-кB activation and inflammatory response in graft after orthotopic liver transplantation in rats

AIM:To study the mechanism and effect of nuclear factor-κB (NF-κB) activation and inflammatory response on theextended cold-preserved graft injury after orthotopic livertransplantation (OLT).METHODS:OLT was performed in rats with varying time ofcold ischemia grafts (6,18 and 24 h in University Wisconsinsolution at 4℃).We determined the time of NF-κB activationand expression of tumor necrosis factor-α (TNF-α),cytokine-inducible neutrophil chemoattractant (CINC),and intercellularadhesion molecule-1 (ICAM-1) within 6 h after reperfusion.Serum alarming aminotransferase (ALT),neutrophilsequestration,circulating neutrophil CD11b and L- selectinexpression were also evaluated.RESULTS:The accumulation of neutrophils in the graft wassignificantly increased in the 18 h and 24 h cold-ischemiagroups within 0.5 h after reperfusion,compared with the 6 hgroup.But the strongly activated neutrophils was slightlyincreased at 2 h after reperfusion and remained at highlevels 4 h after reperfusion,which was synchronized withthe common situation of recipients after transplantation.Prolonged cold-preservation did not affect neutrophilaccumulation and activation.NF-κB activation preceded theexpression of TNF-α,CINC,and ICAM-1 in the liver,whichwas significantly increased with prolonged cold preservation.In prolonged cold preserved grafts,prominently elevatedNF-κB activation occurred at 0.5 h and 1 h,compared withthat at 2 h after reperfusion,which was consistent withgreatly increased intrahepatic TNF-α response.CONCLUSION:NF-κB activation is correlated with theexpression of TNF-α,CINC,and ICAM-1 in vivo in OLT rats.Extended cold preservation of grafts might up-regulate TNF-α,CINC,and ICAM-1 expression in the grafts,most probablythrough elevated NF-κB activation,and might contribute toneutrophil infiltration in the grafts after reperfusion.ElevatedNF-κB activity is harmful to inflammatory response in thegrafts,and inhibited NF-κB activity might protect againstearly graft injury after liver transplantation.