| First Author | Sultan M | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 9 | Pages | e0184084 |
| PubMed ID | 28953903 | Mgi Jnum | J:246753 |
| Mgi Id | MGI:5921914 | Doi | 10.1371/journal.pone.0184084 |
| Citation | Sultan M, et al. (2017) Interleukin-1alpha and Interleukin-1beta play a central role in the pathogenesis of fulminant hepatic failure in mice. PLoS One 12(9):e0184084 |
| abstractText | 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)-1alpha and IL-1beta 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-1alpha and IL-1beta in the progression of LPS/GalN-induced FHF. METHODS: WT, IL-1alpha or IL-1beta 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-1alpha and IL-1beta KO mice was longer than that of WT mice. Lower serum liver enzyme levels, demonstrated reduced hepatic injury in the IL-1alpha and IL-1betaKO mice. Histologically detected liver injury and apoptotic hepatocytes were significantly reduced in the IL-1alphaand IL-1betaKO mice compared to WT mice. Reduced hepatic IkB levels and upregulated NFkappaB activity in WT mice remained inhibited in IL-1alpha and IL-1beta KO mice. Hepatic expression levels of TNFalpha and IL-6 were significantly increased in WT mice but not in IL-1alpha and IL-1beta KO mice. CONCLUSIONS: IL-1alpha and IL-1beta play a central role in the pathogenesis of LPS/GalN-induced FHF. These interleukins are associated with the activation of NFkappaB signaling, upregulation of the pro-inflammatory cytokines and liver damage and apoptosis. Since neither IL-1alpha nor IL-1beta depletions completely rescued the phenotype, we believe that IL-1alpha and IL-1beta have a similar and probably complementary role in FHF progression. |
