Induction of long-term liver allograft survival by delayed immunosuppression is dependent on interleukin-10
✍ Scribed by Zhen Fan Yang; Patricia Ngai; Chi Keung Lau; David W. Ho; Ka Ho Tam; Chi Tat Lam; Ronnie T. Poon; Sheung Tat Fan
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 371 KB
- Volume
- 13
- Category
- Article
- ISSN
- 1527-6465
- DOI
- 10.1002/lt.21091
No coin nor oath required. For personal study only.
✦ Synopsis
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 ϩ CD25 ϩ Foxp3 ϩ and CD8 ϩ CD25 ϩ Foxp3 ϩ 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.