A novel anti-rheumatic drug suppresses tumor necrosis factor-alpha and augments interleukin-10 in adjuvant arthritic rats

Tumor necrosis factor-alpha (TNF-alpha) plays an important role in the path ology of rheumatoid arthritis. When N-[1-(4-([4-(pyrimidin-2-yl)piperazin-1 -yl]methyl)phenyl)cyclopropyl]acetamide (Y-39041) (3-30 mg/kg) was orally a dministered to rats with established arthritis from day 15 to day 20, hindp aw volume was significantly reduced. This inhibitory activity of Y-39041 wa s kept up after administration was stopped. On day 17 Y-39041 suppressed li popolysaccharide-induced TNF-alpha and interleukin-6 production in serum at doses of 3-30 mg/kg, and augmented interleukin-10 production at doses of 1 0 and 30 mg/kg. The finding that Y-39041 suppresses TNF-alpha and interleuk in-6 production and augments interleukin-10 production could be beneficial in the therapy of chronic inflammatory diseases. (C) 2000 Elsevier Science B.V. All rights reserved.