Interleukin-1α and Interleukin-1β play a central role in the pathogenesis of fulminant hepatic failure in mice

作者：Maya Sultan, Ziv Ben‐Ari, Rula Masoud, Orit Pappo, Dror Harats, Yehuda Kamari, Michal Safran · 发表于：PLoS ONE · 年份：2017 · DOI：10.1371/journal.pone.0184084 · 被引用次数：51 · 研究领域：Liver Diseases and Immunity、Liver Disease and Transplantation、Liver physiology and pathology

BACKGROUND AND AIMS: Fulminant hepatitis failure (FHF) is marked by the sudden loss of hepatic function, with a severe life-threatening course in persons with no prior history of liver disease. Interleukin (IL)-1α and IL-1β are key inflammatory cytokines but little is known about their role in the development of FHF. The aim of this study was to assess the involvement of IL-1α and IL-1β in the progression of LPS/GalN-induced FHF. METHODS: WT, IL-1α or IL-1β deficient mice were injected with LPS/GalN. Blood and liver tissue were collected at different time points, FHF related pathways were examined. RESULTS: After FHF induction the survival of both IL-1α and IL-1β KO mice was longer than that of WT mice. Lower serum liver enzyme levels, demonstrated reduced hepatic injury in the IL-1α and IL-1βKO mice. Histologically detected liver injury and apoptotic hepatocytes were significantly reduced in the IL-1αand IL-1βKO mice compared to WT mice. Reduced hepatic IkB levels and upregulated NFκB activity in WT mice remained inhibited in IL-1α and IL-1β KO mice. Hepatic expression levels of TNFα and IL-6 were significantly increased in WT mice but not in IL-1α and IL-1β KO mice. CONCLUSIONS: IL-1α and IL-1β play a central role in the pathogenesis of LPS/GalN-induced FHF. These interleukins are associated with the activation of NFκB signaling, upregulation of the pro-inflammatory cytokines and liver damage and apoptosis. Since neither IL-1α nor IL-1β depletions completely rescued the phe...