Interleukin-1beta Inhibition Attenuates Vasculitis in a Mouse Model of Kawasaki Disease.
J Nippon Med Sch
; 86(2): 108-116, 2019.
Article
em En
| MEDLINE
| ID: mdl-31130561
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-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-1ß, 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-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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Interleucina-1beta
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Anticorpos
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Síndrome de Linfonodos Mucocutâneos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article