The Central Role of Interleukin-1 Signalling in the Pathogenesis of Kawasaki Disease Vasculitis: Path to Translation.

Kawasaki disease (KD) manifests as an acute febrile condition and systemic vasculitis, the etiology of which remains elusive. Primarily affecting children under 5 years of age, if untreated KD can lead to a significant risk of coronary artery aneurysms and subsequent long-term cardiovascular sequelae, including myocardial ischemia and myocardial infarction. Intravenous immunoglobulin therapy mitigates the risk of aneurysm formation, but a subset of patients exhibit resistance to this treatment, increasing the susceptibility of coronary artery lesions. Furthermore, the absence of a KD-specific diagnostic test or biomarkers complicates early detection and appropriate treatment. Experimental murine models of KD vasculitis have substantially improved our understanding of the disease pathophysiology, revealing the key roles of the NLRP3 inflammasome and interleukin-1 (IL-1) signalling pathway. This review aims to delineate the pathophysiologic findings of KD while summarising the findings for the emerging key role of IL-1β in its pathogenesis, derived from both human data and experimental murine models, and the translational potential of these findings for anti-IL-1 therapies for children with KD.