ArticleFrontiers in immunology2026
Association of elevated serum active IL-18 levels with cytokine profiles and clinical features in adult-onset still's disease.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Inflammasome-mediated activation of interleukin (IL)-1β and IL-18 plays a key role in the pathogenesis of adult-onset Still's 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-IL-18, free active IL-18, and IL-18 bound to IL-18-binding protein. This study aimed to measure serum active IL-18 levels in patients with AOSD and evaluate their clinical and diagnostic significance. Methods: 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. Results: Serum levels of active IL-18 were significantly higher in patients with AOSD than in those with RA, FMF, and HCs (all p < 0.001). Active IL-18 levels positively correlated with the Pouchot score (p < 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 > 4,231.1 pg/mL; sensitivity, 89.4%; specificity, 92.9%; area under the curve 0.963). Conclusions: 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.
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