IL-6 Revisited: From Rheumatoid Arthritis to CAR T Cell Therapy and COVID-19
Open accessAbstract
The diverse biological activity of interleukin-6 (IL-6) contributes to the maintenance of homeostasis. Emergent infection or tissue injury induces rapid production of IL-6 and activates host defense through augmentation of acute-phase proteins and immune responses. However, excessive IL-6 production and uncontrolled IL-6 receptor signaling are critical to pathogenesis. Over the years, therapeutic agents targeting IL-6 signaling, such as tocilizumab, a humanized anti-IL-6 receptor antibody, have shown remarkable efficacy for rheumatoid arthritis, Castleman disease, and juvenile idiopathic arthritis, and their efficacy in other diseases is continually being reported. Emerging evidence has demonstrated the benefit of tocilizumab for several types of acute inflammatory diseases, including cytokine storms induced by chimeric antigen receptor T cell therapy and coronavirus disease 2019 (COVID-19). Here, we refocus attention on the biology of IL-6 and summarize the distinct pathological roles of IL-6 signaling in several acute and chronic inflammatory diseases.
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Tocilizumab binds the IL-6 binding site of both membrane and soluble IL-6R, blocking classic, trans-, and cluster signaling.
“Tocilizumab, a humanized monoclonal antibody, is determined to bind to the IL-6 binding site of both membrane and soluble IL-6R, thus blocking classic, trans-, as well as cluster signaling [84, 85].”
From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [85]
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- Authors
- Kishimoto, T., & Kang, S.
- Affiliations
- Immunology Frontier Research Center, The University of Osaka (JP)
- Venue
- Annual Review of Immunology
- Publisher
- Annual Reviews
- Published
- 2022-04-26
- Volume
- 40
- Issue
- 1
- Pages
- 323-348
- ISSN
- 0732-0582 (ISSN-L)
- 1545-3278
- OpenAlex
- W4210578884
- Cited by
- 140
- References
- 171
- Citations by year
- 2026: 27 · 2025: 29 · 2024: 45 · 2023: 21 · 2022: 18
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Ono Medical Research Foundation
- Senri Life Science Foundation
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Keywords
- interleukin-6, IL-6 signaling, tocilizumab, rheumatoid arthritis, Castleman disease, juvenile idiopathic arthritis, CAR T-cell therapy, cytokine storm, COVID-19 pandemic, acute phase response, inflammatory diseases, IL-6 receptor
- MeSH terms
- COVID-19, Animals, Arthritis, Rheumatoid, Humans, Signal Transduction, Interleukin-6, Immunotherapy, Adoptive
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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