Correlation of peripheral blood lymphocyte and intragraft cytokine mRNA expression with rejection in orthotopic liver transplantation

Background. Regulation of allograft rejection mediated by CD4(+) T lymphocytes is dependent on the pattern of cytokines produced by these cells. The purpose of this study was to examine liver transplant recipients to determine whether peripheral blood lymphocyte (PBL), intragraft cytokine production, or both correlated with histologic assessment of graft rejection. Methods. PBL and liver biopsy specimens from transplant recipients were examined at varying times after transplantation. Biopsy samples were examined histologically. Messenger RNA was extracted from PBL and liver biopsy specimens and was then amplified by polymerase chain reaction with oligo-specific primer pairs for interleukin (IL)-2, IL-4, IL-6, transforming growth factor-beta, interferon-gamma, and beta-actin. Results. PBL transcription of IL-2, IL-6, and interferon-gamma was significantly increased in transplant recipients with rejection compared with that in recipients without rejection or healthy individuals who did not undergo transplantation (p < 0.05). Equivalent transcription of IL-4 and transforming growth factor-beta was observed in all patients regardless of rejection status. Graft specimens exhibited quantitative increases in IL-2 and interferon-gamma transcription during rejection with increased IL-4 transcription in the absence of rejection. Conclusions. Our data show that specific patterns of peripheral and intragraft cytokine production play a role in the regulation of rejection in liver transplantation.