Infliximab reduces the cytokine-mediated inflammation but does not suppress cellular infiltration of the vessel wall in refractory Kawasaki disease.

Abstract

The aim of our study was to evaluate the efficacy of infliximab for the treatment of patients with refractory Kawasaki disease (KD) and investigate the dynamic changes of cytokines during infliximab treatment. We have performed a study of cytokine and proinflammatory molecule levels in 43 KD patients including 18 responders to IVIG, 14 nonresponders, 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. In eight patients, fever subsided immediately upon infliximab treatment. Four patients, who started infliximab after 12 d of illness, developed coronary artery lesions. Each of the cytokines was elevated before infliximab treatment in all patients. Although serum levels of proinflammatory 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. We show that infliximab is one of the adoptive therapies in refractory KD patients. Different behaviors of proinflammatory 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.

• Authors: Keiichi Hirono, Yasushi Kemmotsu, Helmut Wittkowski, Dirk Foell, Kazuyoshi Saito, Keijirou Ibuki, Kazuhiro Watanabe, Sayaka Watanabe, Keiichirou Uese, Hirokazu Kanegane, Hideki Origasa, Fukiko Ichida, Johhanes Roth, Toshio Miyawaki, Tsutomu Saji
• Journal: Pediatric research (Pediatr Res) Vol. 65 Issue 6 Pg. 696-701 (Jun 2009) ISSN: 1530-0447 [Electronic] United States
• PMID: 19430379 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antibodies, Monoclonal
• Biomarkers
• Cytokines
• Immunoglobulins, Intravenous
• Infliximab

Topics

• Anti-Inflammatory Agents (immunology, therapeutic use)
• Antibodies, Monoclonal (immunology, therapeutic use)
• Biomarkers (metabolism)
• Child
• Child, Preschool
• Cytokines (blood, immunology)
• Endothelium, Vascular (cytology, immunology, pathology)
• Female
• Humans
• Immunoglobulins, Intravenous (immunology, therapeutic use)
• Infant
• Inflammation (drug therapy)
• Infliximab
• Male
• Mucocutaneous Lymph Node Syndrome (drug therapy, immunology, pathology)
• Treatment Outcome