{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:42:47Z","timestamp":1788982967260,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T00:00:00Z","timestamp":1642204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Interleukin 18 (IL-18) is a pro-inflammatory cytokine of the IL-1 family, whose activity is tightly controlled at the level of production, as well as signalization. Notably, it is buffered by its natural inhibitor, IL-18 binding protein (IL-18BP), which is massively present in circulation in normal and in most pathological conditions, thus preventing harmful pro-inflammatory systemic effects of IL-18. IL-18 has long been considered to be involved in the pathophysiology of various inflammatory diseases. However, a first clinical trial using recombinant IL-18BP for the treatment of rheumatoid arthritis and psoriasis gave disappointing results. Direct measurements of unbound, bioactive, free form of circulating IL-18 demonstrated that IL-18 was more specifically involved in adult-onset Still\u2019s disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA) but also in their most severe complication, macrophage activation syndrome (MAS). More importantly, administration of recombinant IL-18BP to patients with AOSD, and sJIA with MAS, showed promising results. This review summarizes available data regarding IL-18 and IL-18BP in AOSD and sJIA in mouse models and humans and shows the importance of IL-18\/IL-18BP imbalance in these conditions, leading to the conclusion that IL-18, particularly free IL-18, may be a useful biomarker in these diseases and an interesting therapeutic target.<\/jats:p>","DOI":"10.3390\/jcm11020430","type":"journal-article","created":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T20:44:00Z","timestamp":1642365840000},"page":"430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The Role of Interleukin 18\/Interleukin 18-Binding Protein in Adult-Onset Still\u2019s Disease and Systemic Juvenile Idiopathic Arthritis"],"prefix":"10.3390","volume":"11","author":[{"given":"Charlotte","family":"Girard-Guyonvarc\u2019h","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University Hospital of Geneva, 1206 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Harel","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University Hospital of Geneva, 1206 Geneva, Switzerland"},{"name":"Department of Pathology and Immunology, School of Medicine, University of Geneva, 1206 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cem","family":"Gabay","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University Hospital of Geneva, 1206 Geneva, Switzerland"},{"name":"Department of Pathology and Immunology, School of Medicine, University of Geneva, 1206 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1128\/iai.61.1.64-70.1993","article-title":"Purification of a Factor Which Provides a Costimulatory Signal for Gamma Interferon Production","volume":"61","author":"Nakamura","year":"1993","journal-title":"Infect. 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