| First Author | Lee Y | Year | 2012 |
| Journal | Circulation | Volume | 125 |
| Issue | 12 | Pages | 1542-50 |
| PubMed ID | 22361326 | Mgi Jnum | J:198098 |
| Mgi Id | MGI:5495387 | Doi | 10.1161/CIRCULATIONAHA.111.072769 |
| Citation | Lee Y, et al. (2012) Interleukin-1beta is crucial for the induction of coronary artery inflammation in a mouse model of Kawasaki disease. Circulation 125(12):1542-50 |
| abstractText | 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)-1beta in KD. We therefore explored the role of IL-1beta 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-1beta and caspase-1 (activated by the inflammasome and required for IL-1beta maturation) in coronary arteritis and evaluated the efficacy of IL-1 receptor antagonist as a potential treatment. LCWE-induced IL-1beta maturation and secretion were dependent on the NLRP3 inflammasome in macrophages. Both caspase-1-deficient and IL-1 receptor-deficient mice were protected from LCWE-induced coronary lesions. Injection of recombinant IL-1beta into caspase-1-deficient mice restored the ability of LCWE to cause coronary lesions in response to LCWE. Furthermore, daily injections of the IL-1 receptor antagonist prevented LCWE-mediated coronary lesions up to 3 days after LCWE injection. CONCLUSIONS: Our results strongly suggest that caspase-1 and IL-1beta play critical roles in the development of coronary lesions in this KD mouse model, blocked by IL-1 receptor antagonist. Therefore, anti-IL-1beta treatment strategies may constitute an effective, more targeted treatment of KD to prevent coronary lesions. |
