Mechanisms by which interleukin-18 binding protein regulates the NLRP3 inflammasome in Kawasaki disease-related coronary artery lesions

Kawasaki disease (KD) is an acute febrile illness characterized by systemic vasculitis, with coronary artery lesion (CAL) representing its most serious complication. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a pivotal role in KD-associated CAL. Upon activation, it cleaves and releases mature interleukin-18 (IL-18) and other proinflammatory cytokines, which propagates downstream inflammatory cascades. IL-18 binding protein (IL-18BP) is an endogenous high-affinity antagonist. Studies have shown that dysregulation of the IL-18/IL-18BP axis, together with aberrant NLRP3 inflammasome activation, contributes to the initiation and progression of coronary artery injury in KD. This review aims to elucidate the positive feedback amplification between IL-18 and the NLRP3 inflammasome in KD-CAL, and the pathways through which IL-18BP regulates the NLRP3 inflammasome by blocking this positive feedback loop, thereby providing a new theoretical basis and potential interventional targets for the treatment of KD.