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

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)-1 alpha and IL-1 beta 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-1 alpha and IL1 beta in the progression of LPS/GalN-induced FHF. Methods WT, IL-1 alpha or IL-1 beta 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-1 alpha and IL-1 beta KO mice was longer than that of WT mice. Lower serum liver enzyme levels, demonstrated reduced hepatic injury in the IL-1 alpha and IL-1 beta KO mice. Histologically detected liver injury and apoptotic hepatocytes were significantly reduced in the IL-1 alpha and IL-1 beta KO mice compared to WT mice. Reduced hepatic I kappa B levels and upregulated NF kappa B activity in WT mice remained inhibited in IL-1 alpha and IL-1 beta KO mice. Hepatic expression levels of TNF alpha and IL-6 were significantly increased in WT mice but not in IL-1 alpha and IL-1 beta KO mice. Conclusions IL-1 alpha and IL-1 beta play a central role in the pathogenesis of LPS/GalN-induced FHF. These interleukins are associated with the activation of NF.B signaling, upregulation of the pro-inflammatory cytokines and liver damage and apoptosis. Since neither IL-1 alpha nor IL-1 beta depletions completely rescued the phenotype, we believe that IL-1 alpha and IL-1 beta have a similar and probably complementary role in FHF progression.