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

AIM: To study the mechanism and effect of nuclear factor-kappaB (NF-kappaB) activation and inflammatory response on the extended cold-preserved graft injury after orthotopic liver transplantation (OLT).

METHODS: OLT was performed in rats with varying time of cold ischemia grafts (6, 18 and 24 h in University Wisconsin solution at 4 degrees ). We determined the time of NF-kappaB activation and expression of tumor necrosis factor-alpha (TNF-alpha), cytokine-inducible neutrophil chemoattractant (CINC), and intercellular adhesion molecule-1 (ICAM-1) within 6 h after reperfusion. Serum alarming aminotransferase (ALT), neutrophil sequestration, circulating neutrophil CD11b and L- selectin expression were also evaluated.

RESULTS: The accumulation of neutrophils in the graft was significantly increased in the 18 h and 24 h cold-ischemia groups within 0.5 h after reperfusion, compared with the 6 h group. But the strongly activated neutrophils was slightly increased at 2 h after reperfusion and remained at high levels 4 h after reperfusion, which was synchronized with the common situation of recipients after transplantation. Prolonged cold-preservation did not affect neutrophil accumulation and activation. NF-kappaB activation preceded the expression of TNF-alpha, CINC, and ICAM-1 in the liver, which was significantly increased with prolonged cold preservation. In prolonged cold preserved grafts, prominently elevated NF-kappaB activation occurred at 0.5 h and 1 h, compared with that at 2 h after reperfusion, which was consistent with greatly increased intrahepatic TNF-alpha response.

CONCLUSION: NF-kappaB activation is correlated with the expression of TNF-alpha, CINC, and ICAM-1 in vivo in OLT rats. Extended cold preservation of grafts might up-regulate TNF-alpha, CINC, and ICAM-1 expression in the grafts, most probably through elevated NF-kappaB activation, and might contribute to neutrophil infiltration in the grafts after reperfusion. Elevated NF-kappaB activity is harmful to inflammatory response in the grafts, and inhibited NF-kappaB activity might protect against early graft injury after liver transplantation.