Interleukin-1beta Inhibition Attenuates Vasculitis in a Mouse Model of Kawasaki Disease
| Autor: | Naohito Ohno, Nobuko Suzuki, Yasuhiko Itoh, Ryosuke Matsui, Mitsuhiro Kamisago, Miharu Akao, Makoto Watanabe, Yoshiaki Hashimoto, Kanae Tsuno, Koji Hashimoto, Ryuji Fukazawa, Yasuhiro Katsube, Noriko Nagi-Miura |
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| Rok vydání: | 2019 |
| Předmět: |
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 |
| Zdroj: | Journal of Nippon Medical School = Nippon Ika Daigaku zasshi. 86(2) |
| ISSN: | 1347-3409 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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