IL-6 in autoimmune disease and chronic inflammatory proliferative disease
Abstract
Interleukin 6 (IL-6), which was originally identified as a B-cell differentiation factor, is now known to be a multifunctional cytokine that regulates the immune response, hematopoiesis, the acute phase response, and inflammation. Deregulation of IL-6 production is implicated in the pathology of several disease processes. The expression of constitutively high levels of IL-6 in transgenic mice results in fatal plasmacytosis, which has been implicated in human multiple myeloma. Increased IL-6 levels are also observed in several diseases, including rheumatoid arthritis (RA), systemic-onset juvenile chronic arthritis (JCA), osteoporosis, and psoriasis. IL-6 is critically involved in experimentally induced autoimmune disease, such as antigen-induced arthritis (AIA), and experimental allergic encephalomyelitis. All these clinical data and animal models suggest that IL-6 plays critical roles in the pathogenesis of autoimmune diseases. Here we review the evidence for the involvement of IL-6 in the pathophysiology of autoimmune diseases and chronic inflammatory proliferative diseases (CIPD) and discuss the possible molecular mechanisms of its involvement.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Interactions between immune cells and non-immune tissues play critical roles in chronic inflammatory diseases and autoimmune diseases.
“Consistently, evidence has indicated that interactions between immune cells and non-immune tissues play critical roles in chronic inflammatory diseases and autoimmune diseases (3, 41, 49–51).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [3]
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 [3]
There is a correlation between IL-6 and the severity of RA and other inflammatory and autoimmune diseases.
“In line with this notion, there is a correlation between IL-6 and the severity of RA and other inflammatory and autoimmune diseases (3, 260, 261).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [3]
Cites
Takeda, K., Kaisho, T., Yoshida, N., Takeda, J., Kishimoto, T., & Akira, S. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.9.4652 · Cited by 584 · see citing works
Hirano, T., Taga, T., Yasukawa, K., Nakajima, K., Nakano, N., Takatsuki, F., Shimizu, M., Murashima, A., Tsunasawa, S., & Sakiyama, F. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.1.228 · Cited by 351 · see citing works
Self-citationRevival of the autoantibody model in rheumatoid arthritis
Hirano, T. (2002) · Nature Immunology · doi:10.1038/ni0402-342 · Cited by 29 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
A cytokine-mediated link between innate immunity, inflammation, and cancer
Lin, W.-W., & Karin, M. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31537 · Cited by 1,940 · see citing works
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
“Among them, IL-6 is a major player in chronic inflammatory diseases, autoimmune diseases, cancer and cytokine storm (1, 3, 10–26).”
BackgroundSelf-citationThe role of JAK/STAT signaling pathway and its inhibitors in diseases.
Xin, P., Xu, X., Deng, C., Liu, S., Wang, Y., Zhou, X., Ma, H., Wei, D., & Sun, S. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106210 · Cited by 1,010 · see citing works
Sleep health: Reciprocal regulation of sleep and innate immunity
Irwin, M. R., & Opp, M. R. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.148 · Cited by 624 · see citing works
Osteoporosis, inflammation and ageing
Ginaldi, L., Di Benedetto, M. C., & De Martinis, M. (2005) · Immunity & Ageing · doi:10.1186/1742-4933-2-14 · Cited by 412 · see citing works
STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor
Wang, Y., van Boxel-Dezaire, A. H. H., Cheon, H., Yang, J., & Stark, G. R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315862110 · Cited by 327 · see citing works
Graham, A. M., Rasmussen, J. M., Rudolph, M. D., Heim, C. M., Gilmore, J. H., Styner, M., Potkin, S. G., Entringer, S., Wadhwa, P. D., Fair, D. A., et al. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.05.027 · Cited by 282 · see citing works
Pelekanou, V., Kampa, M., Kiagiadaki, F., Deli, A., Theodoropoulos, P., Agrogiannis, G., Patsouris, E., Tsapis, A., Castanas, E., & Notas, G. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.3a0914-430rr · Cited by 184 · see citing works
Davis, M. C., Zautra, A. J., Younger, J., Motivala, S. J., Attrep, J., & Irwin, M. R. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.06.013 · Cited by 177 · see citing works
Sawa, S.-I., Kamimura, D., Jin, G.-H., Morikawa, H., Kamon, H., Nishihara, M., Ishihara, K., Murakami, M., & Hirano, T. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052187 · Cited by 176 · see citing works
Self-citationBraun, D. A., Fribourg, M., & Sealfon, S. C. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.386573 · Cited by 168 · see citing works
Bengtsson, A. K., Ryan, E. J., Giordano, D., Magaletti, D. M., & Clark, E. A. (2004) · Blood · doi:10.1182/blood-2003-10-3380 · Cited by 161 · see citing works
Kauwe, J. S. K., Bailey, M. H., Ridge, P. G., Perry, R., Wadsworth, M. E., Hoyt, K. L., Staley, L. A., Karch, C. M., Harari, O., Cruchaga, C., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004758 · Cited by 125 · see citing works
Choi, H., Shin, D. W., Kim, W., Doh, S.-J., Lee, S. H., & Noh, M. (2011) · Toxicology Letters · doi:10.1016/j.toxlet.2010.10.019 · Cited by 88 · see citing works
Yun, A. J., & Lee, P. Y. (2004) · Medical Hypotheses · doi:10.1016/s0306-9877(03)00326-8 · Cited by 76 · see citing works
Cervantes-Llanos, M., Lagumersindez-Denis, N., Marín-Prida, J., Pavón-Fuentes, N., Falcon-Cama, V., Piniella-Matamoros, B., Camacho-Rodríguez, H., Fernández-Massó, J. R., Valenzuela-Silva, C., Raíces-Cruz, I., et al. (2018) · Life Sciences · doi:10.1016/j.lfs.2017.12.032 · Cited by 73 · see citing works
Pentón-Rol, G., Marín-Prida, J., & McCarty, M. F. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210408123807 · Cited by 73 · see citing works
Cho, H. J., Eisenberger, N. I., Olmstead, R., Breen, E. C., & Irwin, M. R. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.23 · Cited by 64 · see citing works
Mohd Effendy, N., Mohamed, N., Muhammad, N., Naina Mohamad, I., & Shuid, A. N. (2012) · Evidence-Based Complementary and Alternative Medicine · doi:10.1155/2012/125761 · Cited by 55 · see citing works
Transcriptomic predictors of inflammation-induced depressed mood
Cho, J. H.-J., Irwin, M. R., Eisenberger, N. I., Lamkin, D. M., & Cole, S. W. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0316-9 · Cited by 54 · see citing works
Hu, D.-N., Chen, M., Zhang, D. Y., Ye, F., McCormick, S. A., & Chan, C.-C. (2011) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.10-6908 · Cited by 33 · see citing works
Pan, X.-Y., Wang, L., You, H.-M., Cheng, M., Yang, Y., Huang, C., & Li, J. (2021) · Laboratory Investigation · doi:10.1038/s41374-021-00531-7 · Cited by 26 · see citing works
Ahmed, S. S., Schattgen, S. A., Frakes, A. E., Sikoglu, E. M., Su, Q., Li, J., Hampton, T. G., Denninger, A. R., Kirschner, D. A., Kaspar, B., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.68 · Cited by 24 · see citing works
Subtoxic levels hydrogen peroxide-induced expression of interleukin-6 by epidermal melanocytes
Yao, L., Hu, D.-N., Chen, M., & Li, S.-S. (2012) · Archives of Dermatological Research · doi:10.1007/s00403-012-1277-6 · Cited by 22 · see citing works
Kruse, J. L., Boyle, C. C., Olmstead, R., Breen, E. C., Tye, S. J., Eisenberger, N. I., & Irwin, M. R. (2022) · Scientific Reports · doi:10.1038/s41598-022-16364-3 · Cited by 22 · see citing works
Zhang, X., Tian, L., Majumdar, A., & Scheller, E. L. (2024) · Comprehensive Physiology · doi:10.1002/j.2040-4603.2024.tb00300.x · Cited by 18 · see citing works
- Authors
- Ishihara, K., & Hirano, T.
- Affiliations
- The University of Osaka (JP)
- RIKEN (JP)
- Corresponding author
- Hirano, Toshio
- ORCID
- Ishihara, Katsuhiko
- Venue
- Cytokine & Growth Factor Reviews
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 13
- Issue
- 4-5
- Pages
- 357-368
- ISSN
- 1359-6101 (ISSN-L)
- OpenAlex
- W2014732115
- Cited by
- 807
- References
- 3
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 34 · 2023: 24 · 2022: 31 · 2021: 38 · 2020: 39 · 2019: 36 · 2018: 39 · 2017: 32 · 2016: 34 · 2015: 43 · 2014: 38 · 2013: 36 · 2012: 51
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cytokine & Growth Factor Reviews (publishedVersion)
- PubMed (publishedVersion)
- 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, autoimmune disease, rheumatoid arthritis, osteoporosis, psoriasis, multiple myeloma, antigen-induced arthritis, experimental autoimmune encephalomyelitis, plasmacytosis, inflammation
- MeSH terms
- Animals, Autoantibodies, Autoimmune Diseases, Chromosomes, Human, Pair 7, Chronic Disease, Diabetes Mellitus, Type 1, DNA-Binding Proteins, Encephalomyelitis, Autoimmune, Experimental, Forecasting, Humans, Inflammation, Lymphocyte Activation, Mice, Inbred Strains, Mice, Transgenic, Plasmacytoma, Polymorphism, Genetic, Inflammatory Bowel Diseases, Signal Transduction, Trans-Activators, Interleukin-6, B-Lymphocyte Subsets, Mice, Knockout, STAT3 Transcription Factor, Mice
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 ›
Are you an author, or do you see a problem with this page? Request a review
