1. Interleukin-1beta Inhibition Attenuates Vasculitis in a Mouse Model of Kawasaki Disease
- Author
-
Naohito Ohno, Nobuko Suzuki, Yasuhiko Itoh, Ryosuke Matsui, Mitsuhiro Kamisago, Miharu Akao, Makoto Watanabe, Yoshiaki Hashimoto, Kanae Tsuno, Koji Hashimoto, Ryuji Fukazawa, Yasuhiro Katsube, and Noriko Nagi-Miura
- Subjects
Male ,Time Factors ,Interleukin-1beta ,Pharmacology ,Mucocutaneous Lymph Node Syndrome ,Antibodies ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Animals ,Candida albicans ,Aorta ,Innate immune system ,biology ,business.industry ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,General Medicine ,medicine.disease ,biology.organism_classification ,Immunity, Innate ,Interleukin-10 ,Interleukin 10 ,Disease Models, Animal ,Mice, Inbred DBA ,030220 oncology & carcinogenesis ,biology.protein ,030211 gastroenterology & hepatology ,Kawasaki disease ,Tumor necrosis factor alpha ,Antibody ,business ,Vasculitis ,Systemic vasculitis ,Signal Transduction - Abstract
Background Kawasaki disease (KD), a systemic vasculitis, is suspected to be related to abnormalities in innate immunity. Based on the important role of IL-1 signaling in innate immunity, we investigated the effects of an anti-IL-1β antibody using a Candida albicans water-soluble fraction (CAWS)-induced mouse model of KD. Methods CAWS (0.5 mg/mouse) was injected intraperitoneally into 5-week-old DBA/2 mice on five consecutive days. An anti-Murine IL-1β antibody (01BSUR) was administered at various doses (2.5, 5.0, and 10.0 mg/kg) and time points (2 days before, same day, and 2, 5, 7, and 14 days after CAWS administration). After 4 weeks, vasculitis in the aortic root was investigated histologically. Cytokines including IL-1β, -6, -10, and TNF-α were also measured. Results Groups administered 01BSUR at all doses showed a significant reduction in the area of vasculitis. In addition, 01BSUR inhibited vasculitis until 7 days after CAWS administration. In the analysis of various time points, the level of IL-6 was lower in all groups compared to the CAWS only group, but the levels of IL-1β, TNFα, and IL-10 were lower when 01BSUR was administered before CAWS. On the other hand, TNFα and IL-10 levels were restored when 01BSUR was administered after CAWS, suggesting that 01BSUR may have additional effects beyond blocking IL-1β signaling. Conclusions The anti-IL-1β antibody significantly attenuated CAWS-induced vasculitis. The mechanism of inhibiting vasculitis is thought to include inhibition of the IL-1β pathway and additional effects beyond blocking IL-1β signaling.
- Published
- 2019