Interleukin-1beta Inhibition Attenuates Vasculitis in a Mouse Model of Kawasaki Disease

• Published in: Journal of Nippon Medical School Vol. 86; no. 2; pp. 108 - 116
• Main Authors: Hashimoto, Yoshiaki, Fukazawa, Ryuji, Nagi-Miura, Noriko, Ohno, Naohito, Suzuki, Nobuko, Katsube, Yasuhiro, Kamisago, Mitsuhiro, Akao, Miharu, Watanabe, Makoto, Hashimoto, Koji, Tsuno, Kanae, Matsui, Ryosuke, Itoh, Yasuhiko
• Format: Journal Article
• Language: English
• Published: Japan The Medical Association of Nippon Medical School 26-04-2019
• Subjects: cytokine profile; interleukin-10; interleukin-1beta; Kawasaki disease; Kawasaki disease model mouse; Kawasaki disease model mouse; cytokine profile; Kawasaki disease; interleukin-10; interleukin-1beta
• ISSN: 1345-4676; 1347-3409
• DOI: 10.1272/jnms.JNMS.2019_86-206

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.