title: Interleukin-1β is crucial for the induction of coronary artery inflammation in a mouse model of Kawasaki disease.
abstract: 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.
  
  
  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 IL-1 receptor-deficient mice were protected from LCWE-induced coronary lesions. Injection of recombinant IL-1β 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-1β play critical roles in the development of coronary lesions in this KD mouse model, blocked by IL-1 receptor antagonist. Therefore, anti-IL-1β treatment strategies may constitute an effective, more targeted treatment of KD to prevent coronary lesions.
authors.affiliation: Los Angeles, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
authors.forename: Youngho
authors.initials: Y
authors.lastname: Lee
authors.forename: Danica J
authors.initials: DJ
authors.lastname: Schulte
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shimada
authors.forename: Shuang
authors.initials: S
authors.lastname: Chen
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Crother
authors.forename: Norika
authors.initials: N
authors.lastname: Chiba
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: Thomas J A
authors.initials: TJ
authors.lastname: Lehman
authors.forename: Moshe
authors.initials: M
authors.lastname: Arditi
mesh_terms: D000818:Animals; D001167:Arteritis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D053583:Interleukin-1beta / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009080:Mucocutaneous Lymph Node Syndrome / Q000209:etiology / Q000378:metabolism / Q000473:pathology*
chemical_list: D053583:Interleukin-1beta