The Dual Role of Innate Immune Response in Acetaminophen-Induced Liver Injury.

Simple Summary: An injury to the liver caused by a drug or its metabolites is referred to as drug-induced liver injury (DILI). The clinical manifestations of DILI are varied, and it may even result in acute liver failure under certain circumstances. Based on findings in the United States and China, Acetyl-para-aminophenol (APAP) may not be the most prevalent cause of DILI, but it is the leading cause of acute liver failure. The study of immune responses in APAP-induced liver injury (AILI) has been making significant progress in recent years. It should be noted, however, that different studies have reported differing results regarding the role played by immune cells in AILI, with some studies indicating they are proinflammatory, while others have showed no effect, or even pro-repair effects. Therefore, we here discuss the mechanisms of the dual role of immune cells in AILI. Acetyl-para-aminophenol (APAP), a commonly used antipyretic analgesic, is becoming increasingly toxic to the liver, resulting in a high rate of acute hepatic failure in Europe and the United States. Excessive APAP metabolism in the liver develops an APAP–protein adduct, which causes oxidative stress, MPTP opening, and hepatic necrosis. HMGB-1, HSP, nDNA, mtDNA, uric acid, and ATP are DMAPs released during hepatic necrosis. DMAPs attach to TLR4-expressing immune cells such KCs, macrophages, and NK cells, activating them and causing them to secrete cytokines. Immune cells and their secreted cytokines have been demonstrated to have a dual function in acetaminophen-induced liver injury (AILI), with a role in either proinflammation or pro-regeneration, resulting in contradicting findings and some research confusion. Neutrophils, KCs, MoMFs, NK/NKT cells, γδT cells, DCs, and inflammasomes have pivotal roles in AILI. In this review, we summarize the dual role of innate immune cells involved in AILI and illustrate how these cells initiate innate immune responses that lead to persistent inflammation and liver damage. We also discuss the contradictory findings in the literature and possible protocols for better understanding the molecular regulatory mechanisms of AILI. [ABSTRACT FROM AUTHOR]