Abstract

Background and aimsFulminant 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.MethodsWT, 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.ResultsAfter 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.ConclusionsIL-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 phenotype, we believe that IL-1α and IL-1β have a similar and probably complementary role in FHF progression.

Highlights

  • Fulminant hepatic failure (FHF) can be a fatal complication of acute hepatic injury and occurs unpredictably

  • Hepatic expression levels of TNFα and IL-6 were significantly increased in wild type (WT) mice but not in IL-1α and IL-1β KO mice

  • IL-1α and IL-1β play a central role in the pathogenesis of LPS/GalN-induced FHF

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Summary

Introduction

Fulminant hepatic failure (FHF) can be a fatal complication of acute hepatic injury and occurs unpredictably. It is a rare clinical entity marked by the sudden onset of hepatic encephalopathy and loss of hepatic function manifested by coagulopathy, jaundice and multisystem organ failure in persons with no prior history of liver disease [1, 2]. FHF has a severe life-threatening course, a major improvement in survival has been reported due to the implementation of complex intensive care unit protocols and emergency liver transplantation [3]. 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. The aim of this study was to assess the involvement of IL-1α and IL1β in the progression of LPS/GalN-induced FHF.

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