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

• Published in: Inflammation 2023-02, Vol.46 (1), p.480-490
• Main Authors: Okada, Seigo, Yasudo, Hiroki, Ohnishi, Yuji, Matsuguma, Chie, Fukano, Reiji, Motonaga, Takahiro, Waniishi, Takako, Hasegawa, Shunji
• Format: Article
• Language: English
• Subjects: Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; Cell death; Children; Coronary artery; Coronary vessels; Cytokines; Endothelial cells; Endothelial Cells - metabolism; Humans; Immunology; Interleukin 6; Interleukin 8; Interleukin-1 Receptor-Like 1 Protein - metabolism; Interleukin-33 - metabolism; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Internal Medicine; Kawasaki disease; Monocyte chemoattractant protein; Monocytes; Mucocutaneous lymph node syndrome; Mucocutaneous Lymph Node Syndrome - complications; Mucocutaneous Lymph Node Syndrome - diagnosis; Mucocutaneous Lymph Node Syndrome - drug therapy; Original Article; Oxidative stress; Pathology; Pharmacology/Toxicology; Rheumatology; Serum levels; Systemic vasculitis; Therapeutic applications; Therapeutic targets
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-022-01753-7

— 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 a DAMP. We studied 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). 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 sST2, IL-6, IL-8, and monocyte chemoattractant protein−1 in HCAECs in a time- and concentration-dependent manner. Moreover, IL-33 induced significantly greater production of IL-6 and IL-8 in HCAECs compared to the condition stimulated with isoconcentration of tumor necrosis factor-α. 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. Graphical abstract