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".
Inflammation has often been considered to be a nonspecific response and to play 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 diseases. 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 two subtypes of JIA (poly-JIA and systemic JIA), anti-TNF-α monoclonal antibody (infliximab) for children with Kawasaki disease, and anti-IL-1-β 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.
Department of Pediatrics, Yokohama City University School of Medicine , Kanagawa , Japan.
Shumpei
S
Yokota
Masako
M
Kikuchi
Tomo
T
Nozawa
Taichi
T
Kanetaka
Tomomi
T
Sato
Kazuko
K
Yamazaki
Nodoka
N
Sakurai
Ryoki
R
Hara
Masaaki
M
Mori
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000276:immunology; D002648:Child; D002986:Clinical Trials as Topic; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D016207:Cytokines
Kawasaki disease; cryopyrin-associated periodic syndrome; inflammation; innate immunity; systemic-onset juvenile idiopathic arthritis