Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice
Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice
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DOI：
10.1053/jhep.2000.7881
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发表时间：
2000-06-01
期刊：
影响因子：
13.5
通讯作者：
Devière, J
中科院分区：
文献类型：
--
作者：
Le Moine, O;Louis, H;Devière, J
库普弗细胞被认为介导了肝脏缺血再灌注损伤的大部分有害影响。肝脏 T 细胞的作用以及白细胞介素 10 (IL-10) 导致驻留细胞失活的影响从未得到解决。使用离体肝脏冷缺血和再灌注模型，我们评估了 balb/c 小鼠、裸鼠、T 细胞重建裸鼠和钆 balb/c 预处理小鼠肝脏的肝损伤、肿瘤坏死因子 (TNF) 和干扰素 γ (IFN-γ) 释放。然后使用抗炎细胞因子 IL-10 来确定可能能够调节缺血再灌注损伤的最佳给药策略。为此目的，在肝脏收获前、冷缺血期间或再灌注期间的保存介质中向供体施用IL-10。冷保存肝脏再灌注后，TNF 和 IFN-γ 的释放呈时间依赖性且与肝损伤平行。裸鼠或钆预处理小鼠的再灌注肝脏显示 TNF 和 IFN-γ 释放显着减少。在没有 T 细胞的情况下，组织损伤减少了 51%，在库普弗细胞失活时，组织损伤减少了 88%。通过将 T 细胞转移到裸鼠体内，这种效应得以恢复。仅在再灌注期间用IL-10或IL-10输注进行供体预处理可导致肝损伤、TNF和IFN-γ释放显着减少（分别为-66%或-41%、-95%或-94%以及-70%或-70%）。总之，肝脏驻留 T 细胞在冷缺血再灌注损伤中发挥着重要作用，用 IL-10 对供体进行预处理可减少肝损伤以及 T 细胞和巨噬细胞依赖性细胞因子的释放。
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.