Liver regeneration induced by a designer human IL‐6/ sIL‐6R fusion protein reverses severe hepatocellular injury
Abstract
The cytokine IL‐6 plays a significant role in liver regeneration in conjunction with additional growth factors (HGF, TNF‐a, and TGF‐a). Many IL‐6 effects depend on a naturally occurring soluble IL‐6 receptor (sIL‐6R). Here, the chimeric protein hyper‐IL‐6, constructed from the human IL‐6 protein fused to a truncated form of its receptor, was found to have superagonistic IL‐6 properties, and as such, enhanced liver cell regeneration. Hyper‐IL‐6 reversed the state of hepatotoxicity and enhanced the survival rates of rats suffering from fulminant hepatic failure after D‐galac‐tosamine administration. The hyper‐IL‐6 protein has a significant potential for use in the treatment of severe human liver diseases.—Galun, E., Zeira, E., Pappo, O., Peters, M., Rose‐John, S. Liver regeneration induced by a designer human IL‐6/sIL‐6R fusion protein reverses severe hepatocellular injury. FASEB J. 14, 1979–1987 (2000)
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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 [26]
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- Authors
- Galun, E., Zeira, E., Pappo, O., Peters, M., & Rose-John, S.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Hadassah Medical Center (IL)
- Johannes Gutenberg University Mainz (DE)
- Department of Pathology Hadassah University Hospital Jerusalem Israel
- Corresponding author
- Galun, Eithan
- ORCID
- Galun, Eithan
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2000-10
- Volume
- 14
- Issue
- 13
- Pages
- 1979-1987
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2021645238
- Cited by
- 124
- References
- 37
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 12 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 7 · 2013: 6 · 2012: 2
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- liver regeneration, interleukin-6, soluble IL-6 receptor, hyper-IL-6, hepatocyte injury, acute liver failure, D-galactosamine hepatotoxicity
- MeSH terms
- Animals, Cell Division, Disease Models, Animal, Galactosamine, Humans, Liver Regeneration, Male, Rats, Inbred F344, Recombinant Fusion Proteins, Thioacetamide, Interleukin-6, Liver Failure, Apoptosis, Receptors, Interleukin, Receptors, Interleukin-6, Rats
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