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Circulating monocytes accelerate acute liver failure by IL-6 secretion in monkey.

  • Author(s): Guo, Gang
  • Zhu, Yongjie
  • Wu, Zhenru
  • Ji, Hongjie
  • Lu, Xufeng
  • Zhou, Yongjie
  • Li, Yuanmin
  • Cao, Xiaoyue
  • Lu, Yanrong
  • Talbot, Prue
  • Liao, Jiayu
  • Shi, Yujun
  • Bu, Hong
  • et al.
Abstract

Acute liver failure (ALF) is associated with high mortality, and a poor understanding of the underlying pathophysiology has resulted in a lack of effective treatments so far. Here, using an amatoxin-induced rhesus monkey model of ALF, we panoramically revealed the cellular and molecular events that lead to the development of ALF. The challenged monkeys with toxins underwent a typical course of ALF including severe hepatic injury, systemic inflammation and eventual death. Adaptive immune was not noticeably disturbed throughout the progress of ALF. A systematic examination of serum factors and cytokines revealed that IL-6 increase was the most rapid and drastic. Interestingly, we found that IL-6 was mainly produced by circulating monocytes. Furthermore, ablation of monocyte-derived IL-6 in mice decreased liver injury and systemic inflammation following chemical injection. Our findings reveal a critical role of circulating monocytes in initiating and accelerating ALF, indicating a potential therapeutic target in clinical treatment for ALF.

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