Interleukin-33/ST2 Axis as Potential Biomarker and Therapeutic Target in Kawasaki Disease

Abstract

Background：Kawasaki disease（KD）is an acute, self-limiting, febrile systemic vasculitis of unknown cause associated with the development of coronary artery lesions（CALs）during childhood. Alarmin from cell death have been shown to be involved in the development of KD vasculitis. Interleukin（IL）-33 is released from damaged endothelial cells and acts as an alarmin.

Methods：We investigated whether IL-33 and its receptor（ST2）might be involved in KD pathogenesis. Serum levels of soluble ST2（sST2）in KD patients were measured before their first therapy. Furthermore, we investigated the impact of IL-33 on human coronary artery endothelial cells（HCAECs）and human coronary artery smooth muscle cells（HCASMCs）．

Results：Serum levels of sST2 were significantly higher in KD patients with CALs than in those with normal coronary arteries. In vitro, IL-33 upregulated the expression of ST2L and increased production of proinflammatory cytokines in HCAECs in a time- and concentration-dependent manner. Notably, compared to isoconcentration of tumor necrosis factor-α, IL-33 significantly increased IL-6 production. Moreover, IL-1β increases IL-33 production by HCASMCs in a concentration-dependent manner.

Conclusions：The results of our study suggest that the IL-33/ST2 system might be involved in the development of KD vasculitis and a therapeutic target in KD.