Pathogenesis of Systemic Inflammatory Diseases in Childhood: Ã¢ÂÂ Lessons From Clinical Trials of Anti-Cytokine Monoclonal Antibodies for Kawasaki Disease, Systemic Onset Juvenile Idiopathic Arthritis, and Cryopyrin- Associated Periodic Fever Syndrome Ã¢ÂÂShumpei Yokota*, Masako Kikuchi, Satoshi Nozawa, Taichi Kanetaka, Tomoyuki Imagawa, Takako Miyamae, and Masaaki Mori
Department of Pediatrics, Yokohama City University School of Medicine, Japan
- *Corresponding Author:
- Professor Shumpei Yokota
Department of Pediatrics
Yokohama City University School of Medicine
3-9 Fuku-ura, Kanazawa-ku, Yokohama
Kanagawa 236-0004, Japan
E-mail: [email protected]; [email protected]
Received date: July 01, 2013; Accepted date: September 24, 2013; Published date: September 26, 2013
Citation: Yokota S, Kikuchi M, Nozawa S, Kanetaka T, Imagawa T, et al. (2013) Pathogenesis of Systemic Inflammatory Diseases in Childhood: “Lessons From Clinical Trials of Anti-Cytokine Monoclonal Antibodies for Kawasaki Disease, Systemic Onset Juvenile Idiopathic Arthritis, and Cryopyrin-Associated Periodic Fever Syndrome”. Pediat Therapeut 3:171. doi: 10.4172/2161-0665.1000171
Copyright: © 2013 Yokota S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Inflammation has often been considered a non-specific response, and to play only a bridging role in the activation of adaptive immunity. However, it is now accepted that inflammation is the product of an independent innate immune system closely linked to the adaptive immune system. The key mediators of inflammation are inflammatory cytokines, as determined by multiple lines of evidence both in vitro and in vivo. Due to the crucial role of inflammatory cytokines in the pathogenesis of autoimmune disorders, anti-cytokine treatment has been developed as a therapy for rheumatoid arthritis, juvenile idiopathic arthritis (JIA), and inflammatory bowel disease. We recently completed several clinical trials of anti-cytokine treatment for children with systemic inflammatory diseases: anti-IL-6 receptor monoclonal antibody (tocilizumab) for children with 2 subtypes of JIA (poly-JIA and systemic JIA), anti-TNF-alpha monoclonal antibody (infliximab) for children with Kawasaki disease, and anti-IL-1-beta monoclonal antibody (canakinumab) for children with cryopyrin-associated periodic syndrome. This review summarizes the basis of inflammation in terms of innate immunity and adaptive immunity in these systemic inflammatory diseases, clinical efficacy and tolerability of these biologic agents, and attempts to determine the roles of individual inflammatory cytokines in disease pathogenesis.