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.
Keywords: acetyl-para-aminophenol-induced liver injury; cytokine; innate immune response; macrophages; neutrophils.