ASSESSMENT OF THE CYTOKINE RESPONSE IN LIVER-DONORS AT THE TIME OF ORGAN PROCUREMENT AND ASSOCIATION WITH ALLOGRAFT FUNCTION AFTER ORTHOTOPIC TRANSPLANTATION

BACKGROUND: The cause of allograft liver dysfunction after transplanta tion is unresolved. We tested the hypothesis that human donor liver ma y be predisposed to ischemia reperfusion injury, and graft dysfunction subsequent to ongoing inflammatory processes during donor hospitaliza tion. STUDY DESIGN: A prospective study of organ donors and transplant recipients of allogaft livers from these donors was conducted. Portal venous, inferior vena caval, and superior vena caval blood samples we re obtained from 16 clinical organ donors at the time of organ procure ment (one to 12 days post-trauma) to characterize the hepatic cytokine and acute phase protein response, to determine whether or not this re sponse resulted from bacterial or endotoxin translocation to the porta l circulation, and to assess whether or not transplant outcome was ass ociated with plasma levels of cytokines in the donor. RESULTS: In comp arison with systemic blood samples from ten healthy persons, all 16 do nors exhibited significantly (p<0.05) elevated plasma concentrations o f interleukin-6, interleukin-8, soluble p55 tumor necrosis factor rece ptor type I (sTNFr-I), and C-reactive protein. No concentration differ ences existed among portal venous, inferior vena caval, and superior v ena caval blood samples for any cytokine or acute phase protein measur ed. Donor levels of endotoxin, TNF-alpha, soluble intercellular adhesi on molecule-1 (sICAM-1), alpha(1)-acid glycoprotein, alpha(1)-antitryp sin, and haptoglobin were comparable with those in the healthy persons . Bacterial cultures of portal blood were negative. There was no assoc iation between the causation of donor trauma and either donor cytokine response or function and quality of the allograft liver after transpl antation. Nor could an association between donor cytokine response and either early allogaft function (less than 96 hours) or eventual trans plant outcome in the recipients be detected. CONCLUSIONS: These result s indicate that, although an ongoing inflammatory response to injury w as evident in these donors at the time of organ procurement, there wer e no apparent adverse effects arising from these inflammatory processe s on the function and quality of the donor liver after transplantation . Bacterial translocation does not seem to be a component of the patho genesis of inflammation. Whether or not the presence of inflammation i n the donor alters the metabolic responses of the allograft liver and recipient to transplant operation is unknown.