-Original-

Candesartan Attenuates Vasculitis in a Mouse Model of Kawasaki Disease Induced by Candida albicans Water-Soluble Fraction

Ryosuke Matsui¹, Ryuji Fukazawa¹, Ryohei Fukunaga¹, Yusuke Motoji², Yoshiaki Hashimoto¹, Makoto Watanabe¹, Noriko Nagi-Miura³ and Yasuhiko Itoh¹

¹Department of Pediatrics, Nippon Medical School, Tokyo, Japan
²Department of Cardiovascular Surgery, Kitasato University School of Medicine, Kanagawa, Japan
³Center for the Advancement of Pharmaceutical Education, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

Background: The standard treatment for Kawasaki disease is immunoglobulin therapy, but the high frequency of coronary sequelae in immunoglobulin-refractory cases indicates a need for further improvement in treatment.
Methods: Kawasaki disease-like vasculitis was induced in 5-week-old DBA/2 mice by intraperitoneal administration of 0.5 mg Candida albicans water-soluble fraction (CAWS) daily for 5 days followed by daily administration of candesartan, an angiotensin receptor blocker. The vasculitis suppression effect was confirmed histologically and serologically in mice sacrificed at 28 days after the start of candesartan.
Results: The area of inflammatory cell infiltration at the aortic root was 2.4±1.4% in the Control group, 18.1±1.9% in the CAWS group, and 7.1±2.3%, 5.8±1.4%, 7.6±2.4%, and 7.9±5.0% in the CAWS+candesartan 0.125-mg/kg, 0.25-mg/kg, 0.5-mg/kg, and 1.0-mg/kg groups, respectively (p=0.0200, p=0.0122, p=0.0122, and p=0.0200 vs. CAWS, respectively). The low-dose candesartan group also showed significantly reduced inflammatory cell infiltration. A similar trend was confirmed by immunostaining of macrophages and TGFβ receptors. Measurement of the inflammatory cytokines IL-1β, IL-6, and TNF-α confirmed the anti-vasculitis effect of candesartan.
Conclusions: Candesartan inhibited vasculitis even at clinical doses used in children, making it a strong future candidate as an additional treatment for immunoglobulin-refractory Kawasaki disease.

J Nippon Med Sch 2024; 91: 285-295

Keywords
Kawasaki disease, Candida albicans water-soluble fraction (CAWS), angiotensin receptor blocker, candesartan, Kawasaki disease model mouse

Correspondence to
Ryuji Fukazawa, Department of Pediatrics, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
oraora@nms.ac.jp

Received, November 27, 2023
Accepted, January 5, 2024