IL-32γ inhibits acetaminophen-induced acute hepatotoxicity through inactivation of NF-κB and STAT1 signals

Although several studies have shown physiological functions of interleukin (IL)-32, the role of IL-32 in liver has not yet been reported. This study was initiated to examine the effects of IL-32γ on APAP-induced acute hepatic failure in IL-32γ transgenic mice. IL-32γ overexpressing and non-transgenic mice received 500 mg/kg Acetoaminophen (APAP) intraperitoneally. Serum alanine transaminase and aspartate transaminase were significantly lower in the APAP treated IL-32γ overexpressing mice compared with those APAP-treated non-transgenic. IL-32γ markedly reduced a restricted area of the necrosis and inflammation. APAP-induced reduced glutathione depletion, induction of nitric oxide and lipid peroxidation, and cytochrome P4502E1 expression was significantly lowered in the IL-32γ overexpressing mice. Elevation of Kupffer cells and natural killer cells by APAP were reduced in the IL-32γ overexpressing mice. The expression of IL-1α, IL-1ra, macrophage inflammatory protein-2, C-C motif chemokine ligand 5 and tissue inhibitor of metalloproteinase-1 was increased by APAP in nontransgenic mice, and were lowered in the IL-32γ overexpressing mice. Moreover, APAP-induced nuclear transcription factor-kappa B (NF-κB) and signal transducers and activators of transcription 1 (STAT1) activities were greatly lowered in the IL-32γ overexpressing mice. The results indicate that IL-32γ could effectively inhibit drug-induced hepatic failure, and reduce the number of cytotoxic immune cells and pro-inflammatory cytokine production through reduced activities of NF-κB and STAT1. This might be attributable to lowering APAP-induced liver toxicity in IL-32γ overexpressing mice.