Interleukin-1β Is Crucial for the Induction of Coronary Artery Inflammation in a Mouse Model of Kawasaki Disease

Background—Kawasaki disease (KD) is the most common cause of acute vasculitis and acquired cardiac disease in US children. Untreated, children may develop coronary artery aneurysms, myocardial infarction, and sudden death as a result of the illness. Up to a third of KD patients fail to respond to intravenous immunoglobulin, the standard therapy, and alternative treatments are being investigated. Genetic studies have indicated a possible role for interleukin (IL)-1β in KD. We therefore explored the role of IL-1β in a murine model of KD. Methods and Results—Using an established mouse model of KD that involves injection of Lactobacillus casei cell wall extract (LCWE), we investigated the role of IL-1β and caspase-1 (activated by the inflammasome and required for IL-1β maturation) in coronary arteritis and evaluated the efficacy of IL-1 receptor antagonist as a potential treatment. LCWE-induced IL-1β maturation and secretion were dependent on the NLRP3 inflammasome in macrophages. Both caspase-1–deficient and...