Abstract Body (Do not enter title and authors here): Objective: Alarmins resulting from cell death or oxidative stress have been shown to be involved in the development of Kawasaki disease (KD) vasculitis. In our previous study, we demonstrated the potential role of (IL)-33 as an alarmin in the development of KD vasculitis. Although edematous dissociation (necrotic change) of the tunica media is thought to be a major source of IL-33 in KD vasculitis, it has not yet been elucidated.
Methods: We investigated the impact of IL-33 released from necrotic human coronary artery smooth muscle cells (HCASMCs) on human coronary artery endothelial cells (HCAECs) by a co-culture assay using the Transwell^® cell culture insert system. Subsequently, we evaluated the anti-inflammatory effects of anti-IL-33 and anti-ST2 antibodies compared to the conventional therapies of KD, such as high-dose IgG or anti-tumor necrosis factor (TNF)-α antibody.
Results: Primary necrosis of HCASMCs induced significant release of IL-33. In co-cultures of necrotic HCASMCs with HCAECs, necrotic HCASMCs significantly induced the production of various proinflammatory cytokines in HCAECs. Anti-IL-33 and anti-ST2 antibodies exhibited unique inhibitory effects on the production of platelet-derived growth factor-BB or IL-12(p70) in HCAECs.
Conclusion: The results of the present study suggest the potential involvement of edematous dissociation of the tunica media in the development of KD vasculitis. Furthermore, the distinctive anti-inflammatory effects of the anti-IL-33/ST2 axis drugs suggest novel therapeutic options for patients with refractory KD.