Combined interleukin 6 and soluble interleukin 6 receptor accelerates murine liver regeneration
Open accessAbstract
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.
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Although IL-6 classic signaling promotes compensatory hepatocyte proliferation, IL-6 trans-signaling is more important in liver regeneration.
“Although the classic or cis-signaling of IL-6 is determined to promote the compensatory proliferation of hepatocytes, its trans-signaling in liver regeneration is more important [19, 25–27].”
From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [25]
The Discussion (page unavailable) reports that IL-6 combined with soluble IL-6R accelerated hepatocyte proliferation and liver regeneration after partial hepatectomy in mice, whereas IL-6 alone did not significantly accelerate either outcome. This supports the comparison favoring trans-signaling in that model, but the paper does not establish that classic signaling itself promotes compensatory hepatocyte proliferation or that trans-signaling is generally more important across liver regeneration settings. (LLM, conf=0.85)
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- Authors
- Peters, M., Blinn, G., Jostock, T., Schirmacher, P., Büschenfelde, K. M. Z., Galle, P. R., & Rose–John, S.
- Affiliations
- University of Cologne (DE)
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 119
- Issue
- 6
- Pages
- 1663-1671
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W1989052869
- Cited by
- 129
- References
- 36
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 4 · 2023: 8 · 2022: 3 · 2021: 12 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 5 · 2016: 1 · 2015: 6 · 2014: 2 · 2013: 4 · 2012: 5
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- interleukin-6, soluble IL-6 receptor, liver regeneration, partial hepatectomy, hyper-IL-6, gp130 signaling, hepatocyte proliferation, acute liver failure, cytokine fusion proteins
- MeSH terms
- Animals, Cell Division, DNA-Binding Proteins, Gene Expression Regulation, Hepatectomy, Humans, Liver, Liver Regeneration, Mice, Inbred C57BL, Organ Size, Phosphorylation, Postoperative Period, Solubility, Time Factors, Trans-Activators, Interleukin-6, Receptors, Interleukin-6, STAT3 Transcription Factor, Mice
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