Interleukin 6 and its receptor: ten years later
Abstract
Ten years have passed since the molecular cloning of interleukin 6 (IL-6) in 1986. IL-6 is a typical cytokine, exhibiting functional pleiotropy and redundancy. IL-6 is involved in the immune response, inflammation, and hematopoiesis. The IL-6 receptor consists of an IL-6 binding alpha chain and a signal transducer, gp130, which is shared among the receptors for the IL-6 related cytokine subfamily. The sharing of a receptor subunit is a general feature of cytokine receptors and provides the molecular basis for the functional redundancy of cytokines. JAK tyrosine kinase is a key molecule that can initiate multiple signal-transduction pathways by inducing the tyrosine-phosphorylation of the cytokine receptor, gp130 in the case of IL-6, on which several signaling molecules are recruited, including STAT, a signal transducer and activator of transcription, and SHP-2, which links to the Ras-MAP kinase pathway. JAK can also directly activate signaling molecules such as STAT and Tec. These multiple signal-transduction pathways intimately regulate the expression of several genes including c-myc, c-myb, junB, IRF1, egr-1, and bcl-2, leading to the induction of cell growth, differentiation, and survival. The deregulated expression of IL-6 and its receptor is involved in a variety of diseases.
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IL-6 is a major player in chronic inflammatory diseases, autoimmune diseases, cancer and cytokine storm.
“Among them, IL-6 is a major player in chronic inflammatory diseases, autoimmune diseases, cancer and cytokine storm (1, 3, 10–26).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [1]
IL-6 is a pleiotropic cytokine involved in immune responses, inflammation, hematopoiesis, bone metabolism, embryonic development and other fundamental processes.
“IL-6, which was discovered in 1986 (27), is a pleiotropic cytokine involved not only in immune responses but also in inflammation, hematopoiesis, bone metabolism, embryonic development and other fundamental processes (1, 21, 28–32).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [1]
These multiple signal transduction pathways intimately regulate cell survival, proliferation, inflammation, immunity, angiogenesis, and tumor development and progression through the expression of several genes.
“These multiple signal transduction pathways intimately regulate cell survival, proliferation, inflammation, immunity, angiogenesis, and tumor development and progression through the expression of several genes (1, 19, 21, 26, 31).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [1]
Hyper-activation of the immune system to the target tissue may be a consequent event initiated by local initiators in non-immune target tissue in a manner dependent on genetic and/or environmental factors.
“Instead, hyper-activation of the immune system to the target tissue may be a consequent event that is initiated by local initiators in non-immune target tissue in a manner dependent on genetic and/or environmental factors (1, 47, 48, 50).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [1]
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References 215 · Cited by 788
- Authors
- Hirano, T.
- Affiliations
- The University of Osaka (JP)
- Corresponding author
- Hirano, Toshio
- Venue
- International Reviews of Immunology
- Publisher
- Informa UK Limited
- Published
- 1998-01
- Volume
- 16
- Issue
- 3-4
- Pages
- 249-284
- ISSN
- 0883-0185 (ISSN-L)
- 1563-5244
- OpenAlex
- W2111034338
- Cited by
- 788
- References
- 215
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 18 · 2023: 34 · 2022: 23 · 2021: 27 · 2020: 21 · 2019: 14 · 2018: 18 · 2017: 24 · 2016: 33 · 2015: 28 · 2014: 31 · 2013: 36 · 2012: 34
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Reviews of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- interleukin-6, IL-6 receptor, gp130, STAT signaling, SHP2, RAS/MAPK pathway, Tec kinase, cytokine signaling, inflammation, hematopoiesis, gene expression regulation, c-Myc, MYB, JunB, IRF1, EGR1, Bcl-2
- MeSH terms
- Animals, Humans, Signal Transduction, Interleukin-6, Receptors, Interleukin-6, Mice
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