IL-6: From its discovery to clinical applications
Abstract
In the late 1960s, the essential role of T cells in antibody production was reported. This led to our hypothesis that T-cell-derived soluble factors would have to be involved in the activation of B cells. The factor that induced B cells to produce immunoglobulins was initially named B-cell stimulatory factor-2. In 1986, we successfully cloned the complementary DNA encoding B-cell stimulatory factor-2, now known as IL-6. At the same time, IFN-beta2 and a 26-kDa protein found in fibroblasts were independently cloned and found to be identical to IL-6. Later, a hybridoma/plasmacytoma growth factor and a hepatocyte-stimulating factor were also proven to be the same molecule as IL-6. Now, we know that IL-6 is a pleiotropic cytokine with a wide range of biological activities in immune regulation, hematopoiesis, inflammation and oncogenesis. Since the discovery of IL-6, we have further clarified its activities, the IL-6R system and the IL-6 signal transduction mechanism. On the basis of the findings, a new therapeutic approach to block the actions of IL-6 by use of a humanized anti-IL-6R antibody has been proven to be therapeutically effective for rheumatoid arthritis, systemic juvenile idiopathic arthritis and Castleman's disease. In this review, I discuss the history of IL-6 research as a paradigm of progress from basic science to clinical applications.
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As a pro-inflammatory cytokine, IL-6 is produced at local tissue sites by various cells.
“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 [1]
Interleukin-6 plays an important role in both the acute-phase response against infections and liver regeneration.
“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 [1]
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Self-citationPathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease
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“As a pro-inflammatory cytokine IL-6 is produced at local tissue sites by various cells [1,2].”
- Authors
- Kishimoto, T.
- Affiliations
- The University of Osaka (JP)
- Corresponding author
- Kishimoto, T.
- ORCID
- Kishimoto, T.
- Venue
- International Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-04-21
- Volume
- 22
- Issue
- 5
- Pages
- 347-352
- ISSN
- 0953-8178 (ISSN-L)
- 1460-2377
- OpenAlex
- W2096166085
- Cited by
- 846
- References
- 3
- Citations by year
- 2026: 28 · 2025: 46 · 2024: 34 · 2023: 42 · 2022: 71 · 2021: 73 · 2020: 69 · 2019: 44 · 2018: 52 · 2017: 58 · 2016: 59 · 2015: 53 · 2014: 81 · 2013: 55 · 2012: 36
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Biomedical Innovation
- Chugai Pharmaceutical
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- interleukin-6, B cell stimulatory factor 2, IL-6 receptor, rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease, B cell activation, hematopoiesis, inflammation, carcinogenesis
- MeSH terms
- Animals, B-Lymphocytes, Humans, Research, Interleukin-6, History, 20th Century, History, 21st Century
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