13 - INTERLEUKIN-33 FROM NECROTIC TUNICA MEDIA PLAYS A KEY ROLE IN THE DEVELOPMENT OF CORONARY ARTERY LESIONS IN KAWASAKI DISEASE

Background: 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 findings, we demonstrated a potential role for interleukin (IL)-33 as an alarmin in the development of KD vasculitis. Although edematous dissociation (necrotic change) of the tunica media is thought to be one of the major sources of IL-33 in KD vasculitis, little is known on this matter.

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 co-culturing necrotic HCASMCs and live HCAECs without direct cell-to-cell contact. A total of 98 cytokines in cell culture supernatants of HCAECs were analyzed using the BioPlex 3D system.

Results: IL-33 was released from necrotic HCASMCs. Necrotic HCASMCs significantly induced the production of proinflammatory cytokines. In co-cultures of HCAECs with necrotic HCASMCs, both anti-IL-33 and anti-ST2 antibodies showed unique anti-inflammatory effects compared to intravenous immunoglobulin.

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 observed with anti-IL-33/ST2 axis drugs propose novel therapeutic options for refractory KD.