Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice

Authors

  • Olivier Le Moine M.D.,

    Corresponding author
    1. Departments of Gastroenterology, Hopital Erasme, Brussels, Belgium
    2. Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, ULB, Brussels, Belgium
    • Department of Gastroenterology, 808 route de lennik, 1070 Brussels, Belgium. fax: (32) 2 555 46 97
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  • Hubert Louis,

    1. Departments of Gastroenterology, Hopital Erasme, Brussels, Belgium
    2. Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, ULB, Brussels, Belgium
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  • Anne Demols,

    1. Departments of Gastroenterology, Hopital Erasme, Brussels, Belgium
    2. Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, ULB, Brussels, Belgium
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  • Fabrice Desalle,

    1. Laboratory of Experimental Immunology, Université Libre de Bruxelles, ULB, Brussels, Belgium
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  • François Demoor,

    1. Laboratory of Experimental Immunology, Université Libre de Bruxelles, ULB, Brussels, Belgium
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  • Eric Quertinmont,

    1. Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, ULB, Brussels, Belgium
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  • Michel Goldman,

    1. Immunology, Hopital Erasme, Brussels, Belgium
    2. Laboratory of Experimental Immunology, Université Libre de Bruxelles, ULB, Brussels, Belgium
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  • Jacques Devière

    1. Departments of Gastroenterology, Hopital Erasme, Brussels, Belgium
    2. Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, ULB, Brussels, Belgium
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Abstract

Kupffer cells are thought to mediate most of the deleterious effects of liver ischemia-reperfusion injury. The role of liver T cells and the impact of resident cell deactivation by interleukin 10 (IL-10) have never been addressed. Using a model of ex vivo liver cold ischemia and reperfusion, we assessed liver injury, tumor necrosis factor (TNF) and interferon gamma (IFN-γ) release from livers of balb/c mice, nude mice, nude mice reconstituted with T cells, and gadolinium balb/c pretreated mice. The anti-inflammatory cytokine IL-10 was then used to define the best strategy of administration potentially able to modulate ischemia-reperfusion injury. For this purpose IL-10 was administered to the donor before liver harvesting, in the preservation medium during cold ischemia or during reperfusion. TNF and IFN-γ were released time dependently and paralleled liver injury after reperfusion of cold preserved livers. Reperfused livers from nude or gadolinium pretreated mice disclosed a dramatic decrease in TNF and IFN-γ release. Tissue injury was reduced by 51% in the absence of T cells and by 88% when Kupffer cells were deactivated. This effect was reverted by T-cell transfer to nude mice. Only donor pretreatment with IL-10 or IL-10 infusion during reperfusion led to a significant decrease in liver injury, TNF, and IFN-γ release (−66% or −41%, −95% or −94%, and −70% or −70%, respectively). In conclusion, liver resident T cells are critically involved in cold ischemia-reperfusion injury and pretreatment of the donor with IL-10 decreases liver injury and the release of T-cell– and macrophage-dependent cytokines.

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