Since the de-novo synthesis of cytokines by cells kept under ischemic conditions is thought to be quite unlikely, the presence of only marginal concentrations of cytokines during that period in liver transplantation was assumed. This assumption was assessed in the current study. The concentration of cytokines and their soluble receptors were determined by ELISA procedure in serum samples from the donor as well as in perfusates from the right liver vein, obtained by flushing via the portal vein during the preparation of 35 liver grafts in the recipient center. Other serologic parameters were obtained by routine laboratory
Methods: Correlation was assessed using the Spearman Rank Correlation test. The median concentration in the graft perfusate ranged between the 0.2-fold for sIL-6R to the 56-fold (IL-1b) of the donor serum concentration (see table). Strong correlations (r > 0.5; p < 0.01) were found between the concentration of IL-6, IL-1b, TNF-RI and TNF-RII. An increasing release correlating to ischemic time was observed only for TNF-RI, TNF-RII and IL-6 (p < 0.05). The number of leukocytes found in the perfusate correlated to the concentration of TNF-RI, -RII as well as IL-6, whereas the concentration of IL-1b was closely associated to hepatocellular damage indicated by AST and ALT concentrations. A considerable amount of cytokines and receptors was released into the perfusate during the conservation period in liver transplantation. The origin may be leukocytes emerging from the tissue or hepatocytes being damaged. Therefore, intra-graft cytokine levels will have to be included into considerations concerning immunological activation in clinical liver transplantation.
Median concentration of cytokines and soluble receptors in the donor and the graft perfusate
TNF-a [pg/ml] sTNF-RI [ng/ml] sTNF-RII [ng/ml] IL-6 [pg/ml] sIL-6R [ng/ml] IL-1b [pg/ml]
Donor 25.3 3.8 7.0 197 65 0.2
Perfusate 7.3 4.3 5.1 108 11.8 11.2