Interleukin-6 and its receptors: a highly regulated and dynamic system
Abstract
Interleukin-6 (IL-6) is a multifunctional cytokine with well-defined pro- and anti-inflammatory properties. Although only small amounts in the picogram range can be detected in healthy humans, IL-6 expression is highly and transiently up-regulated in nearly all pathophysiological states. IL-6 induces intracellular signaling pathways after binding to its membrane-bound receptor (IL-6R), which is only expressed on hepatocytes and certain subpopulations of leukocytes (classic signaling). Transduction of the signal is mediated by the membrane-bound β-receptor glycoprotein 130 (gp130). In a second pathway, named trans-signaling, IL-6 binds to soluble forms of the IL-6R (sIL-6R), and this agonistic IL-6/sIL-6R complexes can in principle activate all cells due to the uniform expression of gp130. Importantly, several soluble forms of gp130 (sgp130) are found in the human blood, which are considered to be the natural inhibitors of IL-6 trans-signaling. Most pro-inflammatory roles of IL-6 have been attributed to the trans-signaling pathway, whereas anti-inflammatory and regenerative signaling, including the anti-bacterial acute phase response of the liver, is mediated by IL-6 classic signaling. In this simplistic view, only a minority of cell types expresses the IL-6R and is therefore responsive for IL-6 classic signaling, whereas gp130 is ubiquitously expressed throughout the human body. However, several reports point towards a much more complex situation. A plethora of factors, inclu…
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IL-6 transcription is induced by a variety of stimuli, such as Toll-like receptor ligands, IL-1, TNFα, reactive oxygen species and zinc, and also depends on epigenetic regulation.
“IL-6 transcription is induced by a variety of stimuli, such as Toll-like receptor (TLR) ligands, IL-1, TNFα, reactive oxygen species (ROS) and zinc (Zn) and also depends on epigenetic regulation (33, 82, 84–86).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [84]
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- Authors
- Wolf, J., Rose-John, S., & Garbers, C.
- Affiliations
- Christian-Albrechts-Universität zu Kiel (DE)
- Corresponding author
- Garbers, Christoph
- ORCID
- Garbers, Christoph
- Venue
- Cytokine
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 70
- Issue
- 1
- Pages
- 11-20
- ISSN
- 1043-4666 (ISSN-L)
- OpenAlex
- W2001941062
- Cited by
- 618
- References
- 7
- Citations by year
- 2026: 30 · 2025: 63 · 2024: 55 · 2023: 42 · 2022: 59 · 2021: 75 · 2020: 64 · 2019: 41 · 2018: 48 · 2017: 51 · 2016: 48 · 2015: 36 · 2014: 6
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cytokine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- interleukin-6, IL-6 receptor, soluble IL-6 receptor, gp130, trans-signaling, cytokine regulation, acute phase response, hepatocytes, anti-inflammatory signaling, cytokine expression regulation
- MeSH terms
- Humans, Inflammation, Protein Binding, Signal Transduction, Interleukin-6, Models, Immunological, Inflammation Mediators, Receptors, Interleukin-6, Cytokine Receptor gp130
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