{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:26:47Z","timestamp":1778754407096,"version":"3.51.4"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Inflammasome-mediated activation of interleukin (IL)-1\u03b2 and IL-18 plays a key role in the pathogenesis of adult-onset Still\u2019s disease (AOSD), a systemic autoinflammatory disorder. The cleaved free active form of IL-18 may more accurately reflect inflammasome activity than total IL-18, which includes pro\u2013IL-18, free active IL-18, and IL-18 bound to IL-18\u2013binding protein. This study aimed to measure serum active IL-18 levels in patients with AOSD and evaluate their clinical and diagnostic significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum samples were obtained from 47 untreated patients with AOSD, 42 patients with rheumatoid arthritis (RA), 9 patients with familial Mediterranean fever (FMF), and 26 healthy controls (HCs). Active IL-18 was quantified using a specific ELISA detecting cleaved, biologically active IL-18, and 69 cytokines were analyzed in patients with AOSD using a multiplex suspension array. Correlations between active IL-18 and other cytokines, clinical parameters, and the reactive hemophagocytic syndrome diagnostic score (HScore) were evaluated, and discriminative performance was assessed using receiver operating characteristic analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum levels of active IL-18 were significantly higher in patients with AOSD than in those with RA, FMF, and HCs (all p &amp;lt; 0.001). Active IL-18 levels positively correlated with the Pouchot score (p &amp;lt; 0.001), serum ferritin level (p = 0.004), and C-reactive protein level (p = 0.004) and decreased significantly after immunosuppressive therapy (p = 0.003). Active IL-18 significantly and positively correlated with total IL-18, macrophage colony-stimulating factor, basic fibroblast growth factor, leukemia inhibitory factor, chemokine (C-X-C motif) ligand 9, and IL-12 (p40), all of which were significantly correlated with the HScore. Elevated active IL-18 levels were associated with rashes and splenomegaly. Among the evaluated biomarkers, active IL-18 showed the highest diagnostic accuracy for AOSD (cutoff &amp;gt; 4,231.1 pg\/mL; sensitivity, 89.4%; specificity, 92.9%; area under the curve 0.963).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Serum active IL-18 levels were significantly higher in patients with AOSD than in HCs and in patients with FMF or RA. Active IL-18 levels were associated with clinical features such as rash and splenomegaly and correlated with specific cytokines. Serum active IL-18 levels may serve as a biomarker of inflammasome activation and disease activity in patients with AOSD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1759584","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:35:15Z","timestamp":1777354515000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of elevated serum active IL-18 levels with cytokine profiles and clinical features in adult-onset Still\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Shuhei","family":"Yoshida","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Fukushima Medical University School of Medicine","place":["Fukushima, Fukushima, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruki","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Fukushima 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