Abstract 9361: Interleukin-33 System as Potential Biomarker and Therapeutic Target in Kawasaki Disease

Abstract

Introduction: 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. Damage-associated molecular patterns (DAMPs) from cell death and oxidative stress have been shown to be involved in the development of KD vasculitis. Interleukin (IL)-33 is released from damaged endothelial cells and acts as DAMPs. Hypothesis: IL-33 and its receptor (ST2) might be involved in KD pathogenesis. Methods: 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 (87.2 [18.4-224.0] ng/mL vs. 31.7 [8,8-290.3] ng/mL, p = 0.017). In vitro , IL-33 upregulated the expression of ST2L and increased production of sST2, IL-6, IL-8, and monocyte chemoattractant protein–1 in HCAECs in a time- and concentration-dependent manner. Notably, compared to isoconcentration of tumor necrosis factor-α (TNF-α), IL-33 significantly increased IL-6 production; 10 ng/mL of IL-33 increased the production of IL-6 by 13-fold compared with that by TNF-α (9.1 ng/mL vs. 0.7 ng/mL, p < 0.05). Moreover, IL-1β increases IL-33 production by HCASMCs in a concentration-dependent manner. Conclusions: The results of the present study suggest that the IL-33/ST2 axis might be involved in the development of KD vasculitis. The IL-33/ST2 axis may be a therapeutic target for the treatment of KD.