%0 Journal Article
%T A New Phenylpyrazoleanilide, Y-320, Inhibits Interleukin 17 Production and Ameliorates Collagen-Induced Arthritis in Mice and Cynomolgus Monkeys
%A Hiroyuki Ushio
%A Seigo Ishibuchi
%A Koichi Oshita
%A Noriyasu Seki
%A Hirotoshi Kataoka
%A Kunio Sugahara
%A Kunitomo Adachi
%A Kenji Chiba
%J Pharmaceuticals
%D 2014
%I MDPI AG
%R 10.3390/ph7010001
%X Interleukin (IL)-15 and IL-17 are thought to play an important role in the pathogenesis of rheumatoid arthritis (RA) because both pro-inflammatory cytokines are found in synovial fluid of RA patients. In this study, we examined the pharmacological profiles of Y-320, a new phenylpyrazoleanilide immunomodulator. Y-320 inhibited IL-17 production by CD4 T cells stimulated with IL-15 with IC 50 values of 20 to 60 nM. Oral administration of Y-320 (0.3 to 3 mg/kg) significantly inhibited the development and progression of arthritis and joint destruction with reduction of IL-17 mRNA expression in arthritic joints of type II collagen-induced arthritis (CIA) in DBA/1J mice. Y-320 in combination with anti-murine tumor necrosis factor-¦Á monoclonal antibody showed a synergistic effect on mouse CIA. Moreover, therapeutic treatment with Y-320 (0.3 and 1 mg/kg orally) ameliorated CIA in cynomolgus monkeys. Our results suggest that Y-320, an orally active inhibitor for IL-17 production, provides a useful therapy for RA.
%K interleukin 15 (IL-15)
%K interleukin 17 (IL-17)
%K phenylpyrazoleanilide
%K Y-320
%K immunomodulator
%K collagen-induced arthritis (CIA)
%K rheumatoid arthritis (RA)
%U http://www.mdpi.com/1424-8247/7/1/1