{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:30:18Z","timestamp":1791415818836,"version":"4.3.3"},"reference-count":38,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,1,17]]},"abstract":"<jats:p>Interleukin (IL)-1 is a proinflammatory cytokine that plays important roles in inflammation, host defense, and the neuro-immuno-endocrine network. IL-1 receptor antagonist (ra) is an endogenous inhibitor of IL-1 and is supposed to regulate IL-1 activity. However, its pathophysiological roles in a body remain largely unknown. To elucidate the roles of IL-1ra, IL-1ra\u2013deficient mice were produced by gene targeting, and pathology was analyzed on different genetic backgrounds. We found that all of the mice on a BALB\/cA background, but not those on a C57BL\/6J background, spontaneously developed chronic inflammatory polyarthropathy. Histopathology showed marked synovial and periarticular inflammation, with articular erosion caused by invasion of granulation tissues closely resembling that of rheumatoid arthritis in humans. Moreover, elevated levels of antibodies against immunoglobulins, type II collagen, and double-stranded DNA were detected in these mice, suggesting development of autoimmunity. Proinflammatory cytokines such as IL-1\u03b2, IL-6, and tumor necrosis factor \u03b1 were overexpressed in the joints, indicating regulatory roles of IL-1ra in the cytokine network. We thus show that IL-1ra gene deficiency causes autoimmunity and joint-specific inflammation and suggest that IL-1ra is important in maintaining homeostasis of the immune system. Possible involvement of IL-1ra gene deficiency in RA will be discussed.<\/jats:p>","DOI":"10.1084\/jem.191.2.313","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T12:48:33Z","timestamp":1027687713000},"page":"313-320","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":609,"title":["Development of Chronic Inflammatory Arthropathy Resembling Rheumatoid Arthritis in Interleukin 1 Receptor Antagonist\u2013Deficient Mice"],"prefix":"10.1084","volume":"191","author":[{"given":"Reiko","family":"Horai","sequence":"first","affiliation":[{"name":"aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinobu","family":"Saijo","sequence":"additional","affiliation":[{"name":"aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Tanioka","sequence":"additional","affiliation":[{"name":"bDevelopmental Research Laboratories, Santen Pharmaceutical Company Limited, Osaka 533-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Nakae","sequence":"additional","affiliation":[{"name":"aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuko","family":"Sudo","sequence":"additional","affiliation":[{"name":"aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Okahara","sequence":"additional","affiliation":[{"name":"bDevelopmental Research Laboratories, Santen Pharmaceutical Company Limited, Osaka 533-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimi","family":"Ikuse","sequence":"additional","affiliation":[{"name":"bDevelopmental Research Laboratories, Santen Pharmaceutical Company Limited, Osaka 533-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Asano","sequence":"additional","affiliation":[{"name":"aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Iwakura","sequence":"additional","affiliation":[{"name":"aCenter for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","reference":[{"key":"2023072509125064300_R1"},{"key":"2023072509125064300_R2","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1146\/annurev.immunol.14.1.397","article-title":"Role of cytokines in rheumatoid arthritis","volume":"14","author":"Feldmann","year":"1996","journal-title":"Annu. 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