{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:13:14Z","timestamp":1791846794308,"version":"4.3.4"},"reference-count":200,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,9]],"date-time":"2018-11-09T00:00:00Z","timestamp":1541721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science KAKENHI","award":["17K10002"],"award-info":[{"award-number":["17K10002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Interleukein-6 (IL-6), is produced locally from infectious or injured lesions and is delivered to the whole body via the blood stream, promptly activating the host defense system to perform diverse functions. However, excessive or sustained production of IL-6 is involved in various diseases. In diseases, the IL-6 inhibitory strategy begins with the development of the anti-IL-6 receptor antibody, tocilizumab (TCZ). This antibody has shown remarkable effects on Castleman disease, rheumatoid arthritis and juvenile idiopathic arthritis. In 2017, TCZ was proven to work effectively against giant cell arteritis, Takayasu arteritis and cytokine releasing syndrome, initiating a new era for the treatment of these diseases. In this study, the defensive functions of IL-6 and various pathological conditions are compared. Further, the diseases of which TCZ has been approved for treatment are summarized, the updated results of increasing off-label use of TCZ for various diseases are reviewed and the conditions for which IL-6 inhibition might have a beneficial role are discussed. Given the involvement of IL-6 in many pathologies, the diseases that can be improved by IL-6 inhibition will expand. However, the important role of IL-6 in host defense should always be kept in mind in clinical practice.<\/jats:p>","DOI":"10.3390\/ijms19113528","type":"journal-article","created":{"date-parts":[[2018,11,9]],"date-time":"2018-11-09T03:08:02Z","timestamp":1541732882000},"page":"3528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":191,"title":["The Two-Faced Cytokine IL-6 in Host Defense and Diseases"],"prefix":"10.3390","volume":"19","author":[{"given":"Masashi","family":"Narazaki","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan"},{"name":"Department of Immunopathology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadamitsu","family":"Kishimoto","sequence":"additional","affiliation":[{"name":"Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/intimm\/dxq030","article-title":"IL-6: From its discovery to clinical applications","volume":"22","author":"Kishimoto","year":"2010","journal-title":"Int. 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