A Prominent Role of Interleukin-18 in Acetaminophen-Induced Liver Injury Advocates Its Blockage for Therapy of Hepatic Necroinflammation

Frontiers in Immunology
Malte BachmannHeiko Mühl

Abstract

Acetaminophen [paracetamol, N-acetyl-p-aminophenol (APAP)]-induced acute liver injury (ALI) not only remains a persistent clinical challenge but likewise stands out as well-characterized paradigmatic model of drug-induced liver damage. APAP intoxication associates with robust hepatic necroinflammation the role of which remains elusive with pathogenic but also pro-regenerative/-resolving functions being ascribed to leukocyte activation. Here, we shine a light on and put forward a unique role of the interleukin (IL)-1 family member IL-18 in experimental APAP-induced ALI. Indeed, amelioration of disease as previously observed in IL-18-deficient mice was further substantiated herein by application of the IL-18 opponent IL-18-binding protein (IL-18BPd:Fc) to wild-type mice. Data altogether emphasize crucial pathological action of this cytokine in APAP toxicity. Adding recombinant IL-22 to IL-18BPd:Fc further enhanced protection from liver injury. In contrast to IL-18, the role of prototypic pro-inflammatory IL-1 and tumor necrosis factor-α is controversially discussed with lack of effects or even protective action being repeatedly reported. A prominent detrimental function for IL-18 in APAP-induced ALI as proposed herein should rela...Continue Reading

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Citations

Oct 26, 2018·PloS One·Herbert L BonkovskyUNKNOWN US Drug-Induced Liver Injury Network and the Acute Liver Failure Study Group
Jun 28, 2019·The Journal of Experimental Medicine·Michael S Diamond
Jun 20, 2019·The Journal of Experimental Medicine·Serkan BelkayaJean-Laurent Casanova
Apr 26, 2019·Archives of Toxicology·Hellen Karine Paes PortoMatheus Lavorenti Rocha
Apr 15, 2020·Human Genetics·Emmanuelle Jouanguy
Jun 24, 2020·Basic & Clinical Pharmacology & Toxicology·Júlio Cesar AyresMatheus Lavorenti Rocha
Sep 12, 2019·Frontiers in Immunology·Louise BarbierAlice Barbarin
Nov 19, 2020·Cellular & Molecular Immunology·Yong HeBin Gao
May 1, 2021·International Journal of Molecular Sciences·Alessio GerussiPietro Invernizzi

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Methods Mentioned

BETA
pharmacotherapy
PCR

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