The DOI matches its Crossref record; 171 of the 171 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The cited source says what the claim attributes to it.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30183-5 · Cited by 48,884
Clinical characteristics of coronavirus disease 2019 in China
Guan, W.-J., Ni, Z.-Y., Hu, Y., Liang, W.-H., Ou, C.-Q., He, J.-X., Liu, L., Shan, H., Lei, C.-L., Hui, D. S. C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2002032 · Cited by 30,246
Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., Xiang, J., Wang, Y., Song, B., Gu, X., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30566-3 · Cited by 27,263
Dexamethasone in Hospitalized Patients with Covid-19
The RECOVERY Collaborative Group (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2021436 · Cited by 11,477
COVID-19: consider cytokine storm syndromes and immunosuppression
Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., & Manson, J. J. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30628-0 · Cited by 9,664
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312
Wu, C., Chen, X., Cai, Y., Xia, J., Zhou, X., Xu, S., Huang, H., Zhang, L., Zhou, X., Du, C., et al. (2020) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2020.0994 · Cited by 8,249
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992
Endothelial cell infection and endotheliitis in COVID-19
Varga, Z., Flammer, A. J., Steiger, P., Haberecker, M., Andermatt, R., Zinkernagel, A. S., Mehra, M. R., Schuepbach, R. A., Ruschitzka, F., & Moch, H. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30937-5 · Cited by 6,358
Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
Maude, S. L., Frey, N., Shaw, P. A., Aplenc, R., Barrett, D. M., Bunin, N. J., Chew, A., Gonzalez, V. E., Zheng, Z., Lacey, S. F., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1407222 · Cited by 5,413
Research works printed but not linked: 6
- 10.1182/blood.V74.1.1.1 · DOI
- Song Q, 2015, Int. J. Clin. Exp. Med., 8, 15458
- 10.1182/blood.V82.4.1120.1120 · DOI · Paper page
- Dasgupta B, 1992, J. Rheumatol., 19, 22
- Wendling D, 1993, J. Rheumatol., 20, 259
- De Benedetti F, 1997, J. Rheumatol., 24, 1403
Cited by
Sorted by citations
Items 101–141 of 141
Lu, J., Song, J., Yu, H., Gu, G., Zhao, H., Song, F., Zhou, W. L., You, T., & Zhou, J. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115528 · Cited by 1
Exacerbated salmonellosis in poly(ADP-ribose) polymerase 14-deficient mice
Vedantham, M., Polari, L., Rissanen, T., & Pulliainen, A. T. (2025) · Microbiology Spectrum · doi:10.1128/spectrum.02971-25 · Cited by 1
Dang, Q. M., Watanabe, R., Iwasaki, T., Ishihara, R., Kadoba, K., Murata, K., Tanaka, M., Ito, H., Tran, T. D., Quang, S. N. T., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1718591 · Cited by 1
Wu, J., Li, D., Mei, H., & Hu, Y. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.117949 · Cited by 1
Bustos, M., & Rodríguez-Hernández, M. Á. (2026) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2026.120198 · Cited by 1
Refining therapeutic targeting of interleukin-6 by signalling mode selectivity
Rose‐John, S., Waetzig, G. H., & Schreiber, S. (2026) · Nature Reviews Drug Discovery · doi:10.1038/s41573-026-01536-x · Cited by 1
Meng, M., Wu, Y., Sha, W., Zeng, R., Luo, D., Jiang, R., Wu, H., Zhuo, Z., Yang, Q., Li, J., et al. (2023) · Journal of Medical Virology · doi:10.1002/jmv.28720 · Cited by 1
SEVERCAN, S. M., Koca, G., Severcan, Ç., Yılmaz, C., Paşaoğlu, Ö. T., & Paşaoğlu, H. (2023) · Indian Journal of Experimental Biology · doi:10.56042/ijeb.v61i08.3879 · Cited by 1
Elkazzaz, M., Ullah, S., Gao, T., Shamkh, I. M., Ahmed, A. K. K., Wu, T. X., Elsharayidi, M. S., Khan, M. S., Rehman, A.-U., Lotfy, M. M., et al. (2023) · Informatics in Medicine Unlocked · doi:10.1016/j.imu.2023.101323 · Cited by 1
The Role of CCL18 in Rheumatoid Arthritis Diseases
Yuebin, T. (2025) · IgMin Research · doi:10.61927/igmin280 · Cited by 1
Yang, P., Song, Y., & Li, M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1530753 · Cited by 2
Ribeiro, L. T. C., Ribeiro, L. T. C., Landoni, G., Quintão, V. C., Lacerda, M., Rizk, S. I., Costa, I. B. S. D. S., Andrade, F. T. D. A., Melo, E. D. S. A., Neto, N. C. D. S., et al. (2023) · medRxiv · doi:10.1101/2023.12.22.23300466 · Cited by 1
Amin, M. A., Khan, I. I., Nahin, S., Bonna, A. S., Afrin, S., Das, S. P., & Hawlader, M. D. H. (2022) · doi:10.22541/au.164791948.84586726/v1
Li, H., Song, W., Wu, J., Shi, Z., Gao, Y., Li, J., Han, L., Zhang, J., Li, Z., Li, Y., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24062570
REVMATOİD ARTRİTİN MÜALİCƏSİNDƏ İL-6 ƏLEYHİNƏ MONOKLONAL ANTİCİSİMLƏRİN TƏTBİQİNİN PERSPEKTİVLƏRİ
Nasonov, E. L. (2022) · Azerbajdžanskij medicinskij žurnal · doi:10.34921/amj.2022.4.023
Early Prediction and Warning of MODS Following Major Trauma via Identification of Cytokine StormPreprint
Chang, P., Li, R., Wen, J., Jin, F., Yu, Y., Li, Y., Zhang, G., & Wang, T. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.5014158
Rafeeqi, T. A., Pandith, R. A., Humma, H., Shah, A., Zakir, M., Anjum, N., Ara, I., & Ahmed, N. Z. (2025) · Journal of Herbal Medicine · doi:10.1016/j.hermed.2025.100999 · Cited by 2
Михайловна, П. И., Lushpaeva, Y. A., Knaub, N. V., Ustinova, E. A., Belikov, O. A., Долгих, М., & Malysheva, T. Y. (2025) · Modern Rheumatology Journal · doi:10.14412/1996-7012-2025-1-57-63
Benezech, A., Gottenberg, J., Degboé, Y., Kruglov, A., Grogan, J. L., Briand‐Mésange, F., Cantagrel, A. G., Ruyssen‐Witrand, A., & Davignon, J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136355
Kuang, N., Liu, J., Hu, Z., Wu, Y., & Peng, R. Y. (2025) · Preventive Medicine Reports · doi:10.1016/j.pmedr.2025.103169
Cho, J. L. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-824465-4.00252-0
Galoppini, G., Garaffoni, C., Lotesoriere, A., Nogarin, F., Bortoluzzi, A., Govoni, M., & Silvagni, E. (2025) · Biologics · doi:10.2147/btt.s555169
Toxicogenomics of rare earth elements: An exploratory analysis focusing on humans and biodiversity
Ellwanger, J. H., Ziliotto, M., & Chies, J. A. B. (2026) · Next research. · doi:10.1016/j.nexres.2026.101403
Zhao, L., Tang, Z., & Zhu, C. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1825206
Wang, J.-W., Xun, J.-J., & Jian, L.-N. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1846052
Jahromi, H. K., Khalafi, V., Mirzaei, V., Ebrahimi-Zadeh, F., Azami, P., Abdolahy, T., & Razeghian‐Jahromi, I. (2026) · Iranian journal of pharmaceutical research · doi:10.5812/ijpr-168324
Promises of co-stimulatory inhibition for durable and repeatable AAV gene therapy
Kuranda, K., Gross, D., & Ronzitti, G. (2026) · Molecular Therapy · doi:10.1016/j.ymthe.2026.06.014
Discovery and design of potent cell surface display elements
Fang, Z., Saskin, J., Lee, S.-H., Zou, C., Xin, S., Huang, X., Pan, X., Dong, C., Abiri, A., Feng, Y., et al. (2026) · Nature Biotechnology · doi:10.1038/s41587-026-03144-x
The long shadow of a short life: How neutrophils confer trained immunity
Liu, F., Chai, J., 楊佩妮, Fu, S., Li, X., Jiang, X., Li, Y., Ji, T., Fu, Y., Hu, H., et al. (2026) · Autoimmunity Reviews · doi:10.1016/j.autrev.2026.104164
Ji, P., Zhao, P., Guo, W., Cai, S., Hunter, D. J., & Mei, Y. (2026) · Chinese Medical Journal · doi:10.1097/cm9.0000000000004273
Novel 1,3-Indanedione Analogues as Anti-Arthritic Agents Targeting Interleukin-6Preprint
Swaroop, A. K., Mariappan, E., Varshini, M. S., Praveen, T. K., Dharmaraj, S., Namboori, P. K. K., JAWAHAR, N., & Selvaraj, J. (2026) · Research Square · doi:10.21203/rs.3.rs-10712619/v1
The role of interleukin 6 in the development of cardiovascular pathology
Nasonov, E. L., Fomicheva, O. A., Baranov, A. A., Попкова, Т. В., & MIu, S. (2026) · Rheumatology Science and Practice · doi:10.47360/1995-4484-2026-335-357 · Cited by 1
Does acute inflammation triggered by infection promote cancer progression?
Valença-Pereira, F., Johnson, B. J., DeGregori, J. V., & Rincón, M. (2026) · PLoS Biology · doi:10.1371/journal.pbio.3003962
Wu, X., Wang, H., Zhang, L., Wang, B., Tan, X., Zhu, L., Nie, J., & Liu, D. (2026) · Microbiology Spectrum · doi:10.1128/spectrum.03825-25
Yi, C., Shi, J., Li, B., Liu, C., Jiang, H., Sun, J., & Mao, X. (2026) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6c08751
The role of interleukin 6 in the development of cardiovascular pathology
Nasonov, E. L., Fomicheva, O. A., & Попкова, Т. В. (2026) · Сибирский журнал клинической и экспериментальной медицины · doi:10.29001/2073-8552-2026-41-3-12-18
Song, H., 邓先兆, Shen, C., Wang, Y., Xi, C., Zhu, Y., Wang, J., Luo, Q., & Qiu, Z. (2026) · Endocrine Related Cancer · doi:10.1530/erc-26-0198
Rieneck, E., Haak, J. R., Asgarov, K., Pallandre, J., Wundrack, N., Ettich, J., Miri, N., Floss, D. M., Scheller, J., Garbers, C., et al. (2026) · Communications Biology · doi:10.1038/s42003-026-11014-0
Mechanisms of action of TNF-α and IL-6 in cancer pain
Jin, X., Liu, J., Ren, D., Zhang, C., Guo, Z., & Yu, F. (2026) · Frontiers in Pain Research · doi:10.3389/fpain.2026.1981570
Metadata
- 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
- Life Sciences › Immunology and Microbiology › Immunology › 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 ›
Are you an author, or do you see a problem with this page? Request a review
