Etanercept Suppresses Arteritis in a Murine Model of Kawasaki Disease: A Comparative Study Involving Different Biological Agents

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-s...

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Main Authors: Ryuji Ohashi, Ryuji Fukazawa, Makoto Watanabe, Hanako Tajima, Noriko Nagi-Miura, Naohito Ohno, Shinichi Tsuchiya, Yuh Fukuda, Shunichi Ogawa, Yasuhiko Itoh
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:International Journal of Vascular Medicine
Online Access:http://dx.doi.org/10.1155/2013/543141
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author Ryuji Ohashi
Ryuji Fukazawa
Makoto Watanabe
Hanako Tajima
Noriko Nagi-Miura
Naohito Ohno
Shinichi Tsuchiya
Yuh Fukuda
Shunichi Ogawa
Yasuhiko Itoh
author_facet Ryuji Ohashi
Ryuji Fukazawa
Makoto Watanabe
Hanako Tajima
Noriko Nagi-Miura
Naohito Ohno
Shinichi Tsuchiya
Yuh Fukuda
Shunichi Ogawa
Yasuhiko Itoh
author_sort Ryuji Ohashi
collection DOAJ
description 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.
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series International Journal of Vascular Medicine
spelling doaj-art-b4ee7099992c4425a9f0eecb4cd6503a2025-02-03T01:26:50ZengWileyInternational Journal of Vascular Medicine2090-28242090-28322013-01-01201310.1155/2013/543141543141Etanercept Suppresses Arteritis in a Murine Model of Kawasaki Disease: A Comparative Study Involving Different Biological AgentsRyuji Ohashi0Ryuji Fukazawa1Makoto Watanabe2Hanako Tajima3Noriko Nagi-Miura4Naohito Ohno5Shinichi Tsuchiya6Yuh Fukuda7Shunichi Ogawa8Yasuhiko Itoh9Department of Pathology, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo 113-8603, JapanDepartment of Pediatrics, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo 113-8603, JapanDepartment of Pediatrics, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo 113-8603, JapanDepartment of Pediatrics, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo 113-8603, JapanLaboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, JapanLaboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, JapanDepartment of Pathology, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo 113-8603, JapanDepartment of Pathology, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo 113-8603, JapanDepartment of Pediatrics, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo 113-8603, JapanDepartment of Pediatrics, Nippon Medical School, 1-1-5 Bunkyo-ku, Sendagi, Tokyo 113-8603, JapanCoronary 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.http://dx.doi.org/10.1155/2013/543141
spellingShingle Ryuji Ohashi
Ryuji Fukazawa
Makoto Watanabe
Hanako Tajima
Noriko Nagi-Miura
Naohito Ohno
Shinichi Tsuchiya
Yuh Fukuda
Shunichi Ogawa
Yasuhiko Itoh
Etanercept Suppresses Arteritis in a Murine Model of Kawasaki Disease: A Comparative Study Involving Different Biological Agents
International Journal of Vascular Medicine
title Etanercept Suppresses Arteritis in a Murine Model of Kawasaki Disease: A Comparative Study Involving Different Biological Agents
title_full Etanercept Suppresses Arteritis in a Murine Model of Kawasaki Disease: A Comparative Study Involving Different Biological Agents
title_fullStr Etanercept Suppresses Arteritis in a Murine Model of Kawasaki Disease: A Comparative Study Involving Different Biological Agents
title_full_unstemmed Etanercept Suppresses Arteritis in a Murine Model of Kawasaki Disease: A Comparative Study Involving Different Biological Agents
title_short Etanercept Suppresses Arteritis in a Murine Model of Kawasaki Disease: A Comparative Study Involving Different Biological Agents
title_sort etanercept suppresses arteritis in a murine model of kawasaki disease a comparative study involving different biological agents
url http://dx.doi.org/10.1155/2013/543141
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