title: Etanercept suppresses arteritis in a murine model of kawasaki disease: a comparative study involving different biological agents.
abstract: Coronary arteritis, a complication of Kawasaki disease (KD), can be refractory to immunoglobulin (IVIG) treatment. To determine the most effective alternative therapy, we compared the efficacy of different agents in a mouse model of KD. Vasculitis was induced by injection of Candida albicans water-soluble fractions (CAWS) into a DBA/2 mouse, followed by administration of IVIG, etanercept, methylprednisolone (MP), and cyclosporine-A (CsA). At 2 and 4 weeks, the mice were sacrificed, and plasma cytokines and chemokines were measured. CAWS injection induced active inflammation in the aortic root and coronary arteries. At 2 weeks, the vasculitis was reduced only by etanercept, and this effect persisted for the subsequent 2 weeks. At 4 weeks, IVIG and CsA also attenuated the inflammation, but the effect of etanercept was more significant. MP exerted no apparent effect at 2 or 4 weeks. The suppressive effect exerted by etanercept on cytokines, such as interleukin- (IL-)6, IL-12, IL-13, and tumor necrosis factor- α (TNF- α ), was more evident than that of others. The extent of arteritis correlated with the plasma TNF- α levels, suggesting a pivotal role of TNF- α in KD. In conclusion, etanercept was most effective in suppressing CAWS-induced vasculitis and can be a new therapeutic intervention for KD.
authors.affiliation: Department of Pathology, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ohashi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Fukazawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hanako
authors.initials: H
authors.lastname: Tajima
authors.forename: Noriko
authors.initials: N
authors.lastname: Nagi-Miura
authors.forename: Naohito
authors.initials: N
authors.lastname: Ohno
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Yuh
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Shunichi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Itoh