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 pathology of rheumatoid arthritis. When N-[1-(4-¿[4-(pyrimidin-2-yl)piperazin-1-yl]methyl¿phenyl)cycloprop yl] acetamide (Y-39041) (3-30 mg/kg) was orally administered to rats with established arthritis from day 15 to day 20, hindpaw volume was significantly reduced. This inhibitory activity of Y-39041 was kept up after administration was stopped. On day 17 Y-39041 suppressed lipopolysaccharide-induced TNF-alpha and interleukin-6 production in serum at doses of 3-30 mg/kg, and augmented interleukin-10 production at doses of 10 and 30 mg/kg. The finding that Y-39041 suppresses TNF-alpha and interleukin-6 production and augments interleukin-10 production could be beneficial in the therapy of chronic inflammatory diseases.
Hisadome
M
M
Research Laboratories, Welfide Corporation, 955 Koiwai, Yoshitomi-cho, Chikujo-gun, 871-8550, Fukuoka, Japan. hisadome@welfide.co.jp
Fukuda
T
T
Sumichika
H
H
Hanano
T
T
Adachi
K
K
D000081:Acetamides / Q000627:therapeutic use*; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D006614:Hindlimb; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000081:Acetamides; D018501:Antirheumatic Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010879:Piperazines; D014409:Tumor Necrosis Factor-alpha; C406663:Y 39041; D016753:Interleukin-10