Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice.
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-gamma) 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-gamma 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-gamma 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-gamma 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.
Le Moine
O
O
Department of Gastroenterology, Hopital Erasme, Brussels, Belgium. olemoine@ulb.ac.be
Louis
H
H
Demols
A
A
Desalle
F
F
Demoor
F
F
Quertinmont
E
E
Goldman
M
M
Devière
J
J
D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism; D015925:Cryopreservation; D005260:Female; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology; D007511:Ischemia / Q000473:pathology*; D007728:Kupffer Cells / Q000502:physiology; D008024:Ligands; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008102:Liver Circulation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D013601:T-Lymphocytes / Q000502:physiology*; D014019:Tissue Donors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D019013:CD40 Antigens; D008024:Ligands; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma