ACUTE LIVER TRANSPLANT REJECTION CORRELATES WITH IN VITRO PRODUCTION OF TUMOR NECROSIS FACTOR ALPHA AND INTERLEUKIN 13

ACUTE LIVER TRANSPLANT REJECTION CORRELATES WITH IN VITRO PRODUCTION OF TUMOR NECROSIS FACTOR ALPHA AND INTERLEUKIN 13
MC Warlé, A Farhan, HJ Metselaar, WCJ Hop, M Kap, S de Rave, J Kwekkeboom, PE Zondervan, JNM IJzermans, HW Tilanus,V Praviça, IV Hutchinson, GJ Bouma Liver Transplant Research Unit, Erasmus Medical Centre Rotterdam, The Netherlands; School of Biological Sciences, University of Manchester, United Kingdom

Identification of patients who are at risk for acute liver transplant rejection will be useful in the choice of individual based immunosuppressive regimens. Since cytokines play a key-role in allograft rejection, we investigated whether inter-individual differences in capacity of stimulated PBMC to produce cytokines are related to the occurrence of acute liver transplant rejection. PBMC, of 30 healthy individuals and 49 liver transplant recipients, collected after transplantation (>/=10 months), were cultured in the presence and absence of Concanavalin A. The production of TNF-alpha, IFN-gamma, IL-10 and IL-13 was measured in supernatant after 1, 2, 3, 4 and 7 days of cell culture. Rejection was defined in 22 patients ('rejectors') as biopsy-proven rejection, treated with high dose prednisolone, occurring within one month after liver transplantation. Patients who never experienced rejection episodes were termed as 'non-rejectors' (n=27). During the period of cell culture rejectors were found to produce significantly higher levels of TNF-alpha (p=0.045) and higher levels of IFN-gamma (p=0.090) and IL-10 (p=0.069) as compared to non-rejectors. In a further multivariate analysis, in wich patients were grouped into high or low producers according to their maximum capacity to produce cytokines, it was found that high/low production of TNF-alpha (p=0.008) and IL-13 (p=0.042) both correlated independently with the occurrence of acute liver transplant rejection. Differential production of TNF-alpha and IL-13 by PBMC of liver transplant recipients after stimulated cell culture is correlated with the occurrence of acute liver transplant rejection.