IL-10/Fc inhibits macrophage function and prolongs pancreatic islet xenograft survival

Ximin Feng, Xin X. Zheng, Shounan Yi, Anne M. Lehnert, Terry B. Strom, Philip J. O'Connell

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28 Scopus citations


Background. Xenograft rejection is a complex response in which macrophages and other effector cells are activated by CD4+ T cells. Initiation and regulation of this response is in part mediated by cytokines. In this study we test the hypothesis that xenograft destruction is an interleukin- (IL) 10 responsive, macrophage-mediated event. Methods. To study the effect of the systemic administration of IL-10 on pancreatic islet xenograft rejection, a fusion protein of IL-10/Fc was used. This immunoligand possesses the bioavailability of IL-10 and the long circulating t1/2 in vivo, characteristic of Ig. Wistar rat islets were transplanted into C57BL6 mice. IL-10/Fc was administered either immediately before transplantation or in the posttransplant period. Results. Both therapeutic protocols prolonged xenograft survival. Macrophage effector function was reduced in IL-10/Fc- treated mice, with a reduced macrophage infiltrate, reduced IL-12 and tumor necrosis factor-α gene expression and reduced serum NO2- levels. Although the number of T cells infiltrating islet grafts was not reduced, T cell effector function was inhibited in IL-10/Fc-treated animals with reduced interferon-γ and IL-4 gene expression, reduced anti-donor cytotoxicity by recipient splenocytes and reduced anti-donor IgG1 antibody production. Ultimate rejection of the xenografts appears to be mediated by a CD4+ T cell dependent mechanism probably as a result of inadequate inhibition of IL-12 production by macrophages. Conclusion. IL-10/Fc prolonged rat pancreatic islet xenograft survival by inhibiting macrophage mediated immune responses. The effectiveness of this agent when administered pretransplant suggests it may have a role as an induction agent with potential clinical application.

Original languageEnglish
Pages (from-to)1775-1783
Number of pages9
Issue number11
StatePublished - 15 Dec 1999
Externally publishedYes


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