2009 Fiscal Year Final Research Report
Analysis of Pathogen Associated Molecular Pattern(PAMP) in the vascular endothelial cell during acute Kawasaki Disease
| Project/Area Number |
20790721
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | University of Toyama |
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Principal Investigator |
HIRONO Keiichi University of Toyama, 附属病院周産母子センター, 助教 (80456384)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 川崎病 / 冠動脈病変(CAL) / 免疫グロブリン大量療法(IVIG) / Pathogen Associated Molecular Pattern(PAMP) / インフリキシマブ |
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| Research Abstract |
Background: Kawasaki disease (KD) is the most common systemic vasculitis syndrome primarily affecting small and medium-sized arteries, particularly the coronary artery. Although treatment with high-dose intravenous immune globulin (IVIG) is now accepted as reducing the incidence of coronary artery lesions (CAL), approximately 15% of the patients do not respond to IVIG treatment. During acute phase of KD, serum levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-α are elevated. Infliximab is a chimeric murin/human IgG1 monoclonal antibody that binds specifically to human TNF-α-1, and which is administered intravenously, is effective in a broad spectrum of immunologic disorders in which inflammation is mediated by TNF-α. Recent studies reported that patients with KD who did not to IVIG, methylprednisolone pulse therapy (IVMP), and were successfully treated with infliximab.
Objective: The aim of our study was to evaluate the efficacy of infliximab for the treatment of p
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atients with refractory Kawasaki disease (KD) and investigate the dynamic changes of cytokines during infliximab treatment.
Methods: We have performed a study of cytokine and pro-inflammatory molecule levels in 43 KD patients including 18 responders to IVIG, 14 non-responders, and 11 patients treated with infliximab. We determined serum levels of soluble TNF receptor I(sTNFR I) and IL-6, as well as VEGF, damage associated molecular pattern(DAMP) molecules; myeloid-related protein(MRP)8/MRP14 and S100A12 sequentially.
Results: In 8 patients fever subsided immediately upon infliximab treatment. Four patients, who started infliximab after 12 days of illness, developed coronary artery lesions. Each of the cytokines was elevated before infliximab treatment in all patients. Although serum levels of pro-inflammatory cytokines decreased dramatically after infliximab treatment, DAMP molecules and VEGF and markers of local tissue damage were not suppressed. In contrast, in IVIG responders all cytokines decreased markedly after IVIG treatment.
Conclusions: We show that infliximab is one of the adoptive therapies in refractory KD patients. Different behaviors of pro-inflammatory cytokines and DAMP molecules and VEGF after infliximab treatment suggest that infliximab is effective for suppression of cytokine-mediated inflammation, but could not completely block local vasculitis. Less
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[Presentation] The efficacy of infliximab treatment and dynamic changes of inflammatory cytokines in patients with refractory Kawasaki disease.2008
Author(s)
Keiichi Hirono, Kazuyoshi Saito, Sayaka Watanbe, Osamu Higuchi, Keijirou Ibuki, Keiichirou Uese, Fukiko Ichida, Hirokazu Kanegane, Toshio Miyawaki, Yasushi Kennmotsu, Tsutomu Saji
Organizer
The 4th International Kawasaki Disease Symposium
Place of Presentation
Taipei
Year and Date
2008-04-11
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