Cited by 141Cytokine Signaling Pathways and InteractionsRheumatoid Arthritis Research and TherapiesAutoimmune and Inflammatory Disorders Research

IL-6 Revisited: From Rheumatoid Arthritis to CAR T Cell Therapy and COVID-19

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Kishimoto, Tadamitsu, Kang, Sujin·2022·Annual Review of Immunology

Abstract

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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Crossref · 10.1146/annurev-immunol-101220-023458

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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].”

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Authors
Kishimoto, T., & Kang, S.
Affiliations
Immunology Frontier Research Center, The University of Osaka (JP)
Venue
Annual Review of Immunology
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
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

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