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IL-6 pathway in the liver: From physiopathology to therapy
Open accessAbstract
Interleukin 6 (IL-6) is a pleiotropic four-helix-bundle cytokine that exerts multiple functions in the body. In the liver, IL-6 is an important inducer of the acute phase response and infection defense. IL-6 is furthermore crucial for hepatocyte homeostasis and is a potent hepatocyte mitogen. It is not only implicated in liver regeneration, but also in metabolic function of the liver. However, persistent activation of the IL-6 signaling pathway is detrimental to the liver and might ultimately result in the development of liver tumors. On target cells IL-6 can bind to the signal transducing subunit gp130 either in complex with the membrane-bound or with the soluble IL-6 receptor to induce intracellular signaling. In this review we describe how these different pathways are involved in the physiology and pathophyiology of the liver. We furthermore discuss how IL-6 pathways can be selectively inhibited and therapeutically exploited for the treatment of liver pathologies.
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“Interleukin-6 (IL-6) plays an important role in both the acute-phase response against infections as well as liver regeneration (Figure 1).”
From The Role of Perioperative Interleukin-6 Serum Levels on Liver Dysfunction and Infectious Complications After Hepatectomy—A Systematic Review (2025) · cites this paper as [2]
In the citing paper
“As a pro-inflammatory cytokine IL-6 is produced at local tissue sites by various cells [1,2].”
From The Role of Perioperative Interleukin-6 Serum Levels on Liver Dysfunction and Infectious Complications After Hepatectomy—A Systematic Review (2025) · cites this paper as [2]
In the citing paper
“Moreover, IL-6 is a major factor in hepatic regeneration [2].”
From The Role of Perioperative Interleukin-6 Serum Levels on Liver Dysfunction and Infectious Complications After Hepatectomy—A Systematic Review (2025) · cites this paper as [2]
In the citing paper
“The acute phase response in the liver usually does not exceed 48 h, after which the organism returns to normal hepatic function, except in chronic states of inflammation [2].”
From The Role of Perioperative Interleukin-6 Serum Levels on Liver Dysfunction and Infectious Complications After Hepatectomy—A Systematic Review (2025) · cites this paper as [2]
In the citing paper
“However, the deletion of il6 gene also impairs the hepatocyte homeostasis and liver regeneration [3–5].”
From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [5]
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“IL‐6 activates downstream pathways primarily via a classic cis‐signaling and trans‐signaling pathway (11).”
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“Over the last decade a myriad of research publications has helped to decipher the contributions of both pathways to the IL6 biological actions (thoroughly summarized in excellent reviews [153,155,157,164]).”
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BackgroundKupffer cells, the limelight in the liver regeneration
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“30,31 Next, we examined the downstream pathway in macrophages that was regulated by IL-6 signaling.”
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“It is produced in liver in response to acute inflammation (Schmidt-Arras and Rose-John 2016).”
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Result
Metadata
- Authors
- Schmidt-Arras, D., & Rose-John, S.
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 64
- Issue
- 6
- Pages
- 1403-1415
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2253819322
- Semantic Scholar
- 475d5a2af141aef15b1a1a8fb6b45473f2ce0e4b
- Cited by
- 881
- References
- 125
- Citations by year
- 2026: 59 · 2025: 106 · 2024: 97 · 2023: 106 · 2022: 121 · 2021: 114 · 2020: 98 · 2019: 72 · 2018: 54 · 2017: 37 · 2016: 17
- FWCI
- 27.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Hepatology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Keywords
- interleukin-6, IL-6 signaling, liver, acute phase response, liver regeneration, hepatic metabolism, gp130, soluble IL-6 receptor, IL-6 inhibition, liver disease treatment, liver tumors
- MeSH terms
- Interleukin-6 Inhibitors, Acute-Phase Reaction, Animals, Humans, Insulin Resistance, Liver, Liver Neoplasms, Liver Regeneration, Signal Transduction, Interleukin-6, Receptors, Interleukin-6, STAT3 Transcription Factor
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