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Induction of long‐term liver allograft survival by delayed immunosuppression is dependent on interleukin‐10
Author(s) -
Yang Zhen Fan,
Ngai Patricia,
Lau Chi Keung,
Ho David W.,
Tam Ka Ho,
Lam Chi Tat,
Poon Ronnie T.,
Fan Sheung Tat
Publication year - 2007
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21091
Subject(s) - immunosuppression , medicine , foxp3 , liver transplantation , il 2 receptor , interleukin 10 , immunology , isograft , antibody , transplantation , cytokine , pharmacology , immune system , t cell
This study aims to investigate the potential role of endogenous interleukin (IL)‐10 in long‐term liver allograft survival induced by delayed immunosuppression (FK506 days 2‐7). Liver transplantation was performed by using Dark Agouti and Lewis rats as donors and recipients, respectively. The delayed immunosuppression protocol induced indefinite allograft survival. A transient upregulation of plasma IL‐10 levels was detected in the nontreatment and FK506 treatment groups. Macrophages were found to be one of the major sources of IL‐10 produced from the liver allografts. Administration of IL‐10–neutralizing antibody shortened the long‐term isograft survival and FK506‐induced indefinite allograft survival, particularly in the FK506 group. Damaged liver graft histology and increase of plasma alanine aminotransferase levels were detected in the groups with IL‐10 antibody treatment. In an ex vivo setting, IL‐10 recombinant protein augmented the expression of Foxp3, downregulated the expression of IL‐2 and interferon gamma, and induced the generation of CD4 + CD25 + Foxp3 + and CD8 + CD25 + Foxp3 + cells, but this effect was blocked by the administration of IL‐10 antibody. Finally, administration of IL‐10 recombinant protein after the decline of endogenous IL‐10 levels improved allograft survival, and a 100% long‐term allograft survival was achieved by the combination of IL‐10 with low‐dose FK506. In conclusion, the delayed immunosuppression could induce long‐term liver allograft survival in the presence of endogenous IL‐10 produced by the tissue macrophages. Supplementary exogenous IL‐10 administration combined with low‐dose immunosuppressive drug may be a useful strategy to induce long‐term liver allograft survival. Liver Transpl 13:571–578, 2007. © 2007 AASLD.