title: Losartan attenuates the coronary perivasculitis through its local and systemic anti-inflammatory properties in a murine model of Kawasaki disease.
abstract: BACKGROUND
  Kawasaki disease is a common systemic vasculitis that leads to coronary artery lesions. Besides its antihypertensive effects, losartan can modulate inflammation in cardiovascular disease. We examined whether losartan can attenuate coronary inflammation in a murine model of Kawasaki disease.
  
  
  RESULTS
  Five-wk-old C57/BL6J male mice were intraperitoneally injected with Lactobacillus casei cell wall extract to induce coronary inflammation and divided into four groups: placebo, intravenous immunoglobulin (IVIG), losartan, and IVIG+losartan. After 2 wk, mice were harvested. The coronary perivasculitis was significantly attenuated by losartan but not by IVIG alone, and further dramatic attenuation by IVIG+losartan was observed. The frequency of Lactobacillus casei cell wall extract-induced myocarditis (80%) was markedly lowered by losartan (22%) and IVIG+losartan (0%). Furthermore, interleukin (IL)-6 mRNA was markedly attenuated by IVIG+losartan. Serum levels of IL-6, TNF-α, MCP-1, and IL-10 after Lactobacillus casei cell wall extract injection were slightly decreased by IVIG or losartan. Moreover, IL-1β, IL-10, and MCP-1 levels were significantly decreased by IVIG+losartan.
  
  
  CONCLUSIONS
  The addition of losartan to IVIG strongly attenuated the severity of coronary perivasculitis and the incidence of myocarditis, along with suppressing systemic/local cytokines as well as the activated macrophage infiltration. Therefore, losartan may be a potentially useful additive drug for the acute phase of Kawasaki disease to minimize coronary artery lesions.
authors.affiliation: Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan.|Division of Infectious Diseases and Immunology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Suganuma
authors.affiliation: Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Niimura
authors.affiliation: Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Ukawa
authors.affiliation: Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Sekine
authors.affiliation: Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kato
authors.affiliation: Laboratory for Infectious Disease, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Aiba
authors.affiliation: Laboratory for Infectious Disease, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Koga
authors.affiliation: Laboratory Center for Clinical Epidemiology, St. Luke's International University, Tokyo, Japan.
authors.forename: Kuniyoshi
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Laboratory Center for Clinical Epidemiology, St. Luke's International University, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takahashi
authors.affiliation: Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mochizuki
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002473:Cell Wall; D018932:Chemokine CCL2 / Q000097:blood; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007249:Inflammation; D007262:Infusions, Intravenous; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007780:Lacticaseibacillus casei; D019808:Losartan / Q000627:therapeutic use*; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014657:Vasculitis / Q000188:drug therapy*
chemical_list: D000889:Anti-Arrhythmia Agents; D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C556062:IL10 protein, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D016753:Interleukin-10; D019808:Losartan