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

被引:116
作者
Peters, M
Blinn, G
Jostock, T
Schirmacher, P
Zum Büschenfelde, KHM
Galle, PR
Rose-John, S
机构
[1] Johannes Gutenberg Univ Mainz, Dept Med 1, Div Pathophysiol, D-6500 Mainz, Germany
[2] Univ Cologne, Inst Pathol, D-5000 Cologne, Germany
关键词
D O I
10.1053/gast.2000.20236
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Liver regeneration after toss 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.
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页码:1663 / 1671
页数:9
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