Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice
Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice
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DOI：
10.1002/hep.510280621
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发表时间：
1998-12-01
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：
Louis, H;Van Laethem, JL;Devière, J
本文研究了抗炎细胞因子白细胞介素-10（IL-10）在四氯化碳（CCl_4）诱导的小鼠肝损伤模型中的作用。为了阐明内源性IL-10产生的作用，在C57 B1/6 IL-10基因敲除（KO）和野生型（WT）小鼠中通过CCl 4诱导急性肝炎。CCl 4激发后，血清和肝脏肿瘤坏死因子-α（TNF-α）水平和血清转化生长因子-β 1（TGF-β 1）水平升高，并且在IL-10 KO小鼠中显著更高，而IL-6血清水平与WT小鼠相比仅略有升高。在组织学上！检查中，肝脏显示在注射CCl 4后12和24小时，IL-10 KO小鼠中显著更显著的嗜酸性浸润。相比之下，肝细胞坏死，通过组织学检查和血清丙氨酸氨基转移酶水平进行评估，只有轻微的影响。与WT小鼠相比，注射CCl 4后48小时，IL-10 KO小鼠的肝细胞增殖反应（通过增殖细胞核抗原标记指数评估）显著增加。最后，重复CCl 4注射导致7周后IL-10 KO小鼠中更多的肝纤维化。总之，内源性IL-10对肝细胞坏死的影响很小，尽管它控制了CCl 4诱导的急性炎症爆发。在肝修复过程中，它限制了肝细胞的增殖反应和纤维化的发展。
The role of the anti-inflammatory cytokine interleukin-10 (IL-10) was investigated in;he mouse model of liver injury induced by carbon tetrachloride (CCl4). To address the role of endogenous IL-10 production, acute hepatitis was induced by CCl4 in C57Bl/6 IL-10 gene knock out (KO) and wild-type (WT) mice. After CCl4 challenge, serum and liver levels of tumor necrosis factor-alpha (TNF-alpha) and serum levels of transforming growth factor-beta 1 (TGF-beta 1) increased and were significantly higher in IL-10 KO mice, whereas IL-6 serum levels were only slightly increased compared with WT mice. At histological! examination, the livers disclosed a significantly more prominent neutrophilic infiltration in IL-10 KO mice 12 and 24 hours after CCl4 injection. In contrast, hepatocyte necrosis, evaluated by histological examination and serum alanine aminotransferase levels, was only marginally affected. The proliferative response of hepatocytes, assessed by the proliferating cell nuclear-antigen labeling index, was significantly increased in IL-10 KO mice, compared with WT mice 48 hours after CCl4 injection. Finally, repeated CCl4 injections led to more liver fibrosis in IL-IO KO mice after 7 weeks. In conclusion, endogenous IL-10 marginally affects the hepatocyte necrosis although it controls the acute inflammatory burst induced by CCl4. During liver repair, it limits the proliferative response of hepatocytes and the development of fibrosis.