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- Title
Interleukin-1beta Inhibition Attenuates Vasculitis in a Mouse Model of Kawasaki Disease.
- Authors
Yoshiaki Hashimoto; Ryuji Fukazawa; Noriko Nagi-Miura; Naohito Ohno; Nobuko Suzuki; Yasuhiro Katsube; Mitsuhiro Kamisago; Miharu Akao; Makoto Watanabe; Koji Hashimoto; Kanae Tsuno; Ryosuke Matsui; Yasuhiko Itoh
- 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-1ß 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-1ß 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-1ß, -6, -10, and TNF-a 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-1ß, TNFa, and IL-10 were lower when 01BSUR was administered before CAWS. On the other hand, TNFa and IL-10 levels were restored when 01BSUR was administered after CAWS, suggesting that 01BSUR may have additional effects beyond blocking IL-1ß signaling. Conclusions: The anti-IL-1ß antibody significantly attenuated CAWS-induced vasculitis. The mechanism of inhibiting vasculitis is thought to include inhibition of the IL-1ß pathway and additional effects beyond blocking IL-1ß signaling.
- Subjects
MUCOCUTANEOUS lymph node syndrome; VASCULITIS; ANTINEUTROPHIL cytoplasmic antibodies; MEDICAL model; NATURAL immunity; MICE
- Publication
Journal of Nippon Medical School, 2019, Vol 86, Issue 2, p108
- ISSN
1345-4676
- Publication type
Article
- DOI
10.1272/jnms.jnms.2019_86-206