Molecule4 diseases

IL-18

Key cytokine uniquely elevated in AOSD; drives MAS and IFN-γ production

Expression change
Markedly elevated (up to 1000-fold)
Evidence level
established
Targeted by
Tadekinig alfa (IL-18BP)

Expression across diseases

DiseaseRoleExpressionEvidence
Adult-Onset Still's DiseaseKey cytokine uniquely elevated in AOSD; drives MAS and IFN-γ productionMarkedly elevated (up to 1000-fold)established
Cryopyrin-Associated Periodic SyndromesInflammasome-derived cytokineelevatedstrong
Familial Mediterranean FeverSecondary inflammasome cytokineElevatedmoderate
Schnitzler SyndromeNK cell activatorElevatedmoderate

Role in pathogenesis

IL-18 serum levels in active AOSD can be up to 1000-fold higher than in other rheumatic diseases — the highest levels reported for any disease. IL-18 drives Th1 polarization, IFN-γ production, macrophage activation, and is closely linked to MAS development. Free IL-18 (not bound to IL-18BP) is specifically elevated in AOSD vs other inflammatory diseases. IL-18 serves as a diagnostic biomarker, disease activity marker, and potential therapeutic target.

Sources (4)

DetailsColafrancesco S et al. (2012) IL-18 Serum Level in Adult Onset Still's Disease: A Marker of Disease ActivityDOI
DetailsGirard C et al. (2016) Elevated serum levels of free interleukin-18 in adult-onset Still's diseasePubMed
DetailsInoue N et al. (2019) Comparative study of interleukin-18 serum levels in adult onset Still's disease and systemic onset juvenile idiopathic arthritisPubMed
DetailsGabay C et al. (2018) Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's diseasePubMed