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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Combined interleukin 6 and soluble interleukin 6 receptor accelerates murine liver regeneration.

BACKGROUND & AIMS: Liver regeneration after loss of hepatic tissue leads to hepatocyte and nonparenchymal cell proliferation and rapid restoration of liver parenchyma. Interleukin (IL)-6 is a key inducer of transcription factors involved in liver regeneration. Whenever IL-6 activates target cells, it binds to a specific IL-6 receptor ( IL-6R). The IL-6/ IL-6R complex then associates with the signal transducer gp130, leading to activation of intracellular signaling. METHODS: We have recently constructed the designer cytokine Hyper-IL-6 consisting of soluble IL-6R covalently linked to IL-6, which directly stimulates gp130 even in the absence of membrane- bound IL-6R. We compared the influence of IL-6 and Hyper-IL-6 on liver regeneration after partial hepatectomy in mice. RESULTS: The IL-6/soluble IL-6 fusion protein Hyper-IL-6, but not IL-6 alone, led to an earlier onset of hepatocellular proliferation resulting in an acceleration of liver weight restoration. Also, during liver regeneration, soluble IL-6R levels were increased. CONCLUSIONS: These results emphasize a central role for IL-6 and soluble IL-6R in liver regeneration and indicate a possible therapeutic potential for the designer cytokine Hyper-IL-6 in clinical situations associated with liver regeneration such as acute hepatic failure or resection of chronically damaged liver tissue.[1]


  1. Combined interleukin 6 and soluble interleukin 6 receptor accelerates murine liver regeneration. Peters, M., Blinn, G., Jostock, T., Schirmacher, P., Meyer zum Büschenfelde, K.H., Galle, P.R., Rose-John, S. Gastroenterology (2000) [Pubmed]
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