Transhepatic neutrophil and monocyte activation during clinical liver transplantation

Background. During experimental liver transplantation, neutrophil sequestra tion results in increased oxygen free radical production and correlates inv ersely with graft viability. Neutrophil activation in clinical liver transp lantation is poorly understood. Methods. We assessed leukocyte sequestration and transhepatic differences o f neutrophil and monocyte CD11b expression, neutrophil free radical product ion, and plasma concentrations of interleukin 6 and interleukin 8 in nine p atients during liver transplantation. Results. Significant hepatic neutrophil sequestration occurred during initi al graft rewarming with portal blood, after inferior vena cava declamping, and after hepatic artery declamping (all P<0.05). A positive transhepatic d ifference (i.e., outcoming - ingoing) in CD11b expression of neutrophils wa s observed after portal vein declamping (51+/-32 relative fluorescence unit [RFU]) and in CD11b expression of monocytes during initial graft rewarming (67+/-86 RFU, both P<0.05). A transcoronary increase in both unstimulated (74+/-80 RFU) and N-formyl-methionyl-leucyl-phenylalanine-stimulated (112+/ -168 RFU) neutrophil free radical production took place after hepatic arter y declamping (both P<0.05). A negative transcoronary difference of interleu kin 6 occurred during initial graft rewarming (-192+/-176 pg/ml) and a posi tive difference of interleukin 8 occurred after hepatic artery declamping ( 17+/-23 pg/ml, both P<0.05). Conclusions. Hepatic sequestration and transhepatic activation of neutrophi ls, and hepatic production of interleukin 8 occur during clinical liver tra nsplantation. A splanchnic influx of interleukin 6 occurs to the graft, pos sibly modulating neutrophil-mediated graft reperfusion injury.