title: In vitro cytokine production of TNFalpha and IL-13 correlates with acute liver transplant rejection.
abstract: Individuals may differ in their capacity to produce cytokines. Since cytokines play a key role in allograft rejection, we investigated whether inter-individual differences in cytokine production by in vitro stimulated PBMC are 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 with high dose prednisolone. Patients who never experienced rejection episodes 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. 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. In cell culture, stimulated PBMC of rejectors were found to produce significantly higher levels of TNF-alpha, while there was a trend towards higher production of IFN-gamma and IL-10 as compared to nonrejectors. After grouping patients into high or low cytokine producers based upon reference levels of the healthy individuals using multivariate analysis it was found that occurrence of acute liver 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.
authors.affiliation: Department of Surgery, Liver Transplant Research Unit, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Warlé
authors.forename: A
authors.initials: A
authors.lastname: Farhan
authors.forename: H J
authors.initials: HJ
authors.lastname: Metselaar
authors.forename: W C
authors.initials: WC
authors.lastname: Hop
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Plas
authors.forename: M
authors.initials: M
authors.lastname: Kap
authors.forename: S
authors.initials: S
authors.lastname: de Rave
authors.forename: J
authors.initials: J
authors.lastname: Kwekkeboom
authors.forename: P E
authors.initials: PE
authors.lastname: Zondervan
authors.forename: J N
authors.initials: JN
authors.lastname: IJzermans
authors.forename: H W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: V
authors.initials: V
authors.lastname: Pravica
authors.forename: I V
authors.initials: IV
authors.lastname: Hutchinson
authors.forename: G J
authors.initials: GJ
authors.lastname: Bouma
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection; D006650:Histocompatibility Testing; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D018793:Interleukin-13; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma