Targeting innate immune responses to attenuate acetaminophen-induced hepatotoxicity

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.