Interleukin 6 is important for survival after partial hepatectomy in mice
Interleukin 6 is important for survival after partial hepatectomy in mice
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DOI：
10.1053/jhep.2003.50378
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发表时间：
2003-09-01
期刊：
影响因子：
13.5
通讯作者：
Heim, MH
中科院分区：
文献类型：
--
作者：
Blindenbacher, A;Wang, XY;Heim, MH
白细胞介素6（IL-6）缺陷小鼠对部分肝切除术（PH）的反应受损。众所周知，IL-6在诱导急性期（AP）反应中的作用，手术和肝切除术后这种反应的损害可以解释缺陷的肝细胞再生。此外，有人提出IL-6在PH后最初2至4小时内刺激静止细胞重新进入细胞周期中具有重要作用。为了进一步分析IL-6的作用，我们在野生型小鼠、IL-6敲除（KO）小鼠、以及在手术前30分钟通过静脉（IV）（短效）或皮下（SC）（长效）注射重组IL-6进行治疗的IL-6 KO小鼠中。IL-6缺陷小鼠的高术后死亡率可以通过SC完全预防，但不能通过IV IL-6治疗，表明需要IL-6的持续作用。然而，有一部分IL-6 KO小鼠即使没有IL-6治疗也能在PH中健康地存活。当我们分析这些小鼠时，我们发现了完整的肝脏再生，没有迹象表明细胞周期重入受阻。我们的结论是，IL-6的主要作用是诱导适应性反应，以PH，确保身体的稳态和生存。
The response to partial hepatectomy (PH) is impaired in interleukin 6 (IL-6)-deficient mice. IL-6 is well known for its role in the induction of the acute phase (AP) response, and the impairment of this response after surgery and hepatectomy could explain the defective hepatocyte regeneration. In addition, it was proposed that IL-6 has an important role in stimulating the reentry of quiescent cells into the cell cycle within the first 2 to 4 hours after PH. To further analyze the role for IL-6, we performed two third hepatectomies in wild-type mice, in IL-6 knockout (KO) mice, and in IL-6 KO mice that were treated 30 minutes before surgery with intravenous (IV) (short acting) or subcutaneous (SC) (long acting) injections of recombinant IL-6. The high postoperative mortality of IL-6 -deficient mice could be completely prevented by SC, but not by IV IL-6 treatment, showing the requirement of a sustained action of IL-6. However, there is a subset of IL-6 KO mice that survives a PH in good health even without IL-6 treatment. When we analyzed these mice, we found an intact liver regeneration and no indication of a block in cell cycle reentry. We conclude that the major role of IL-6 is the induction of an adaptive response to PH that ensures body homeostasis and survival.