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

IF 1.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Journal of Nippon Medical School Pub Date : 2024-01-01 DOI:10.1272/jnms.JNMS.2024_91-307

Ryosuke Matsui, Ryuji Fukazawa, Ryohei Fukunaga, Yusuke Motoji, Yoshiaki Hashimoto, Makoto Watanabe, Noriko Nagi-Miura, Yasuhiko Itoh

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Abstract

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.

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坎地沙坦可减轻白色念珠菌水溶性馏分诱导的川崎病小鼠模型中的血管炎

背景：川崎病的标准治疗方法是免疫球蛋白疗法：川崎病的标准治疗方法是免疫球蛋白疗法，但免疫球蛋白难治性病例中冠状动脉后遗症的发生率很高，这表明需要进一步改进治疗方法：方法：给 5 周大的 DBA/2 小鼠腹腔注射 0.5 毫克白色念珠菌水溶性成分（CAWS），连续 5 天，然后每天注射血管紧张素受体阻滞剂坎地沙坦，诱导川崎病样血管炎。在开始服用坎地沙坦后 28 天，对小鼠进行组织学和血清学检查，以证实其血管炎抑制效果：结果：对照组小鼠主动脉根部炎症细胞浸润面积为 2.4±1.4%，CAWS 组为 18.1±1.9%，CAWS 组为 7.1±2.3%、5.8±1.4%、7.6±2.4% 和 7.9±5.0%。CAWS+坎地沙坦 0.125-mg/kg、0.25-mg/kg、0.5-mg/kg 和 1.0-mg/kg 组分别为 7.1±2.3%、5.8±1.4%、7.6±2.4% 和 7.0±5.0%（与 CAWS 相比分别为 p=0.0200、p=0.0122、p=0.0122 和 p=0.0200）。低剂量坎地沙坦组的炎症细胞浸润也明显减少。巨噬细胞和 TGFβ 受体的免疫染色也证实了类似的趋势。炎症细胞因子IL-1β、IL-6和TNF-α的测定证实了坎地沙坦的抗血管炎作用：坎地沙坦即使在儿童临床剂量下也能抑制血管炎，因此坎地沙坦是未来治疗免疫球蛋白难治性川崎病的有力候选药物。

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来源期刊

Journal of Nippon Medical School MEDICINE, GENERAL & INTERNAL-

CiteScore

1.80

自引率

10.00%

发文量

118

期刊介绍： The international effort to understand, treat and control disease involve clinicians and researchers from many medical and biological science disciplines. The Journal of Nippon Medical School (JNMS) is the official journal of the Medical Association of Nippon Medical School and is dedicated to furthering international exchange of medical science experience and opinion. It provides an international forum for researchers in the fields of bascic and clinical medicine to introduce, discuss and exchange thier novel achievements in biomedical science and a platform for the worldwide dissemination and steering of biomedical knowledge for the benefit of human health and welfare. Properly reasoned discussions disciplined by appropriate references to existing bodies of knowledge or aimed at motivating the creation of such knowledge is the aim of the journal.