Affiliation:
1. Department of Pathology, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan
2. Department of Pediatrics, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo 113-8603, Japan
3. Laboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, Japan
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 ofCandida albicanswater-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-αlevels, suggesting a pivotal role of TNF-αin KD. In conclusion, etanercept was most effective in suppressing CAWS-induced vasculitis and can be a new therapeutic intervention for KD.
Funder
Ministry of Education, Culture, Sports, Science, and Technology
Subject
Cardiology and Cardiovascular Medicine
Cited by
17 articles.
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