Leflunomide inhibits cytokine-induced DNA synthesis of rabbit synovial cells in culture.
The effects of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on DNA synthesis of rabbit synovial cells were studied. IL-1 beta 1000-10,000 U.ml-1, IL-6 10-1000 U.ml-1, TNF alpha 0.5-50 U.ml-1 and GM-CSF 1-100 ng.ml-1 concentration-dependently stimulated DNA synthesis in rabbit synovial cells in culture. Leflunomide (LFM) and its metabolite A77 1726 elicited an inhibitory effect on such cytokine-induced DNA synthesis of synovial cells. These results suggested that IL-1 beta, IL-6, TNF alpha and GM-CSF play a key role in the pathogenesis of rheumatoid arthritis. Inhibition of cytokine-induced proliferation of synovial cells by LFM may partially explain its antirheumatic activity.
Ju
D W
DW
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
Zheng
Q Y
QY
Wang
H B
HB
Fang
J
J
D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003437:Crotonates; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004247:DNA / Q000096:biosynthesis*; D006885:Hydroxybutyrates / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D009570:Nitriles; D011817:Rabbits; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*; D014052:Toluidines
D000814:Aniline Compounds; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003437:Crotonates; D016207:Cytokines; D006885:Hydroxybutyrates; D007555:Isoxazoles; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D004247:DNA; D000077339:Leflunomide