Wang Jincheng, Zhang Lulu, Shi Qi, Yang Bo, He Qiaojun, Wang Jiajia, Weng Qinjie
Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Biochem Pharmacol. 2022 Aug;202:115142. doi: 10.1016/j.bcp.2022.115142. Epub 2022 Jun 11.
Acetaminophen (APAP) hepatotoxicity is an important cause of acute liver failure, resulting in massive deaths in many developed countries. Currently, the metabolic process of APAP in the body has been well studied. However, the underlying mechanism of APAP-induced liver injury remains elusive. Increasing clinical and experimental evidences indicate that the innate immune responses are involved in the pathogenesis of APAP-induced acute liver injury (AILI), in which immune cells have dual roles of inducing inflammation to exacerbate hepatotoxicity and removing dead cells and debris to help liver regeneration. In this review, we summarize the latest findings of innate immune cells involved in AILI, particularly emphasizing the activation of innate immune cells and their different roles during the injury and repair phases. Moreover, current available treatments are discussed according to the different roles of innate immune cells in the development of AILI. This review aims to update the knowledge about innate immune responses in the pathogenesis of AILI, and provide potential therapeutic interventions for AILI.
对乙酰氨基酚（APAP）肝毒性是急性肝衰竭的重要原因，在许多发达国家导致大量死亡。目前，APAP在体内的代谢过程已得到充分研究。然而，APAP诱导肝损伤的潜在机制仍不清楚。越来越多的临床和实验证据表明，固有免疫反应参与了APAP诱导的急性肝损伤（AILI）的发病机制，其中免疫细胞具有双重作用，即诱导炎症以加重肝毒性，以及清除死亡细胞和碎片以帮助肝脏再生。在本综述中，我们总结了参与AILI的固有免疫细胞的最新发现，特别强调固有免疫细胞的激活及其在损伤和修复阶段的不同作用。此外，根据固有免疫细胞在AILI发展中的不同作用，讨论了当前可用的治疗方法。本综述旨在更新关于AILI发病机制中固有免疫反应的知识，并为AILI提供潜在的治疗干预措施。
