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. 1. Introduction Kawasaki disease (KD) is an acute, self-limited febrile illness that mainly occurs in early childhood [1]. Most of the clinical symptoms exhibited by patients with KD are caused by an acute inflammatory response affecting small- to medium-sized vessels located throughout the body [1]. The most common complication involves the coronary arteries, leading to prominent vasculitis and secondary aneurysm formation [2]. The injured coronary arteries occasionally cause thrombosis formation, which in turn induces ischemic heart disease [3]. Although the etiology of KD is currently unknown, the condition likely results from an immunologic response triggered by microbial agent [4]. At present, intravenous administration of immunoglobulin (IVIG) is the gold standard therapy for coronary arteritis in the acute phase of KD [5, 6]. However, some patients do not respond to the IVIG therapy, and coronary aneurysms continue to develop in 5% of the affected children [7]. To treat these IVIG nonresponders, alternative treatments, such as corticosteroids, cyclosporine-A, cyclophosphamide, and plasma pheresis have been tested [8–13]. A recent study indicated that IVIG plus prednisolone therapy significantly reduced the occurrence rate of coronary aneurysms in Japanese
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