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.
方法:通过每天腹膜内给予0.5mg白色念珠菌水溶性部分(CAWS),在5周龄的DBA/2小鼠中诱导川崎病样血管炎,持续5天,然后每天给予坎地沙坦,血管紧张素受体阻滞剂.在坎地沙坦开始后28天处死的小鼠中,在组织学和血清学上证实了血管炎抑制作用。
结果:对照组主动脉根部炎性细胞浸润面积为2.4±1.4%,CAWS组18.1±1.9%,和7.1±2.3%,5.8±1.4%,7.6±2.4%,在CAWS+坎地沙坦0.125-mg/kg中,为7.9±5.0%,0.25-mg/kg,0.5-mg/kg,和1.0-mg/kg组,分别(p=0.0200,p=0.0122,p=0.0122和p=0.0200vs.CAWS,分别)。低剂量坎地沙坦组也显示出炎性细胞浸润显著减少。通过巨噬细胞和TGFβ受体的免疫染色证实了类似的趋势。炎性细胞因子IL-1β的测定,IL-6和TNF-α证实了坎地沙坦的抗血管炎作用。
结论:坎地沙坦即使在儿童临床剂量下也能抑制血管炎,使其成为免疫球蛋白难治性川崎病的额外治疗的强大未来候选药物。