In vitro cytokine production of TNF alpha and IL-13 correlates with acute liver transplant rejection

Individuals may differ in their capacity to produce cytokines. Since cytoki nes play a key role in allograft rejection, we investigated whether inter-i ndividual differences in cytokine production by in vitro stimulated PBMC ar e related to the occurrence of acute liver transplant rejection. Our Study group comprised 49 liver transplant recipients and 30 healthy individuals. Rejection, which occurred within one month after liver transplantation, was defined in 22 patients ("rejectors") as biopsy-proven rejection, treated w ith high dose prednisolone. Patients who never experienced rejection episod es were termed as "nonrejectors" (n = 27). PBMC of healthy individuals and of liver transplant recipients, collected late after transplantation (mean 3.5 years), were cultured in the presence and absence of Concanavalin A. Th e production of TNF-alpha, IFN-gamma, IL-10, and IL-13 was measured in supe rnatant after 1, 2, 3, 4, and 7 days of cell culture. In cell culture, stim ulated PBMC of rejectors were found to produce significantly higher levels of TNF-alpha, while there was a trend towards higher production of IFN-gamm a and IL-10 as compared to nonrejectors. After grouping patients into high or low cytokine producers based upon reference levels of the healthy indivi duals using multivariate analysis it was found that occurrence of acute liv er transplant rejection correlated to high production of TNF-alpha and low production of IL-13. After stimulated cell culture PBMC of liver transplant recipients show a differential production of TNF-alpha and IL-13 which is correlated with the occurrence of acute liver transplant rejection. (C) Ame rican Society for Histocompatibility and Immunogenetics, 2001. Published by Elsevier Science Inc.