Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis
Abstract
High levels of interleukin 6 (IL 6/B cell stimulatory factor-2) were detected in synovial fluids from the joints of patients with active rheumatoid arthritis (RA). The cells found in freshly isolated synovial fluid constitutively expressed IL 6 mRNA. The synovial tissues obtained by joint biopsy were also found to produce IL 6 in vitro. Immunohistochemical analysis demonstrated that CD2+ T cells as well as CD20+ blastoid B cells in the synovial tissues produce IL 6. The data indicate that IL 6 is generated constitutively in RA and its overproduction may explain the local as well as the generalized symptoms of RA, since IL 6 can function as B cell growth and differentiation factor as well as hepatocyte-stimulating factor.
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Increased IL-6 activity is associated with chronic inflammatory diseases including rheumatoid arthritis, multiple sclerosis, and Crohn's disease.
“Increased activity of interleukin (IL)-6 has been associated with chronic inflammatory diseases including rheumatoid arthritis (Hirano et al., 1988), multiple sclerosis (Frei et al., 1991; Navikas et al., 1996), and Crohn's disease (Ito, 2003).”
From Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib (2017) · cites this paper as Hirano et al., 1988
IL-6 is present at high amounts in the synovial fluid of rheumatoid arthritis patients.
“and is present at high amounts in the synovial fluid of rheumatoid arthritis (RA) patients (44, 45)”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [44]
Cites
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IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
“…the 1980s also showed that IL-6 is produced by cardiac myxoma cells (42) and Castleman’s germinal center cells (43) and is present at high amounts in the synovial fluid of rheumatoid arthritis (RA) patients (44, 45), suggesting its role in autoimmune diseases and chronic inflammatory diseases (1).”
BackgroundSelf-citationThe Pathophysiologic Roles of Interleukin-6 in Human Disease
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Pleiotropy and specificity: insights from the interleukin 6 family of cytokines
Murakami, M., Kamimura, D., & Hirano, T. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.027 · Cited by 533 · see citing works
Self-citationHistorical overview of the interleukin-6 family cytokine
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Self-citationIL-6 <i>Trans</i>-Signaling Modulates TLR4-Dependent Inflammatory Responses via STAT3
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Agalactosyl glycoforms of IgG autoantibodies are pathogenic
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“Since then, several pieces of evidence have been reported that suggest the involvement of IL-6 in autoimmune diseases, including RA (4, 17).”
BackgroundSelf-citationInhibition of IL-6 for the treatment of inflammatory diseases
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“In rheumatoid arthritis (RA) patients, a high concentration of IL-6 is detected in the serum and joint fl uids (18).”
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Deep immune phenotyping reveals similarities between aging, Down syndrome, and autoimmunity
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Self-citationMurakami, M., & Hirano, T. (2011) · Frontiers in Immunology · doi:10.3389/fimmu.2011.00022 · Cited by 53 · see citing works
“Moreover, patients with RA show high synovial concentrations of IL-6 (Hirano et al., 1988), while anti-IL-6 receptor therapy is effective for some RA patients (Nakagawa et al., 2010).”
Self-citationSobotta, S., Raue, A., Huang, X., Vanlier, J., Jünger, A., Bohl, S., Albrecht, U., Hahnel, M. J., Wolf, S., Mueller, N. S., et al. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00775 · Cited by 28 · see citing works
“Increased activity of interleukin (IL)-6 has been associated with chronic inflammatory diseases including rheumatoid arthritis (Hirano et al., 1988), multiple sclerosis (Frei et al.”
Background
- Authors
- Hirano, T., Matsuda, T., Turner, M., Miyasaka, N., Buchan, G., Tang, B., Sato, K., Shimi, M., Maid, R., Feldmann, M., & Kishimoto, T.
- Affiliations
- The University of Osaka (JP)
- Corresponding author
- Kishimoto, Tadamitsu
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 1988-11
- Volume
- 18
- Issue
- 11
- Pages
- 1797-1802
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2045590518
- Cited by
- 784
- References
- 1
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 5 · 2023: 10 · 2022: 14 · 2021: 15 · 2020: 9 · 2019: 14 · 2018: 14 · 2017: 21 · 2016: 12 · 2015: 14 · 2014: 24 · 2013: 18 · 2012: 15
- FWCI
- 44.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Keywords
- interleukin-6, B cell stimulatory factor 2, rheumatoid arthritis, synovial fluid, synovium, IL-6 mRNA expression, CD2+ T cells, CD20+ B cells, hepatocyte-stimulating factor, cytokine overproduction
- MeSH terms
- Antigens, Differentiation, B-Lymphocyte, Antigens, Differentiation, T-Lymphocyte, Arthritis, Rheumatoid, Humans, Interleukins, Receptors, Immunologic, RNA, Messenger, Synovial Fluid, Synovial Membrane, Interleukin-6, CD2 Antigens, Antigens, CD20
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