[Leflunomide inhibits PAF induced DNA synthesis in rabbit synovial cells and PAF production from rat peritoneal macrophages].
Leflunomide (LFM, HWA 486) is an isoxazol derivative with antiphogistic and novel immunomodulating properties. It has been shown to be very effective in preventing and curing arthritis. In this report we found that platelet-activating factor (PAF) at 0.1-10 micrograms.ml-1 significantly stimulated DNA synthesis in cultured rabbit synovial cells. While LFM and its metabolite A771726 elicited inhibitory effects on this action of PAF. These two agents were also shown to markedly inhibit A23187 induced PAF production from rat peritoneal macrophages. The inhibition was dose and time-dependent. The inhibitory effects of LFM and A771726 on DNA synthesis in synovial cells and PAF production from macrophages may play an important role in the antiinflammatory effects of LFM.
Ju
D W
DW
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai.
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*; D003437:Crotonates; D004247:DNA / Q000096:biosynthesis*; D006885:Hydroxybutyrates / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D017737:Macrophages, Peritoneal / Q000378:metabolism; D009570:Nitriles; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011817:Rabbits; D051381:Rats; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism; D014052:Toluidines
D000814:Aniline Compounds; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003437:Crotonates; D006885:Hydroxybutyrates; D007555:Isoxazoles; D009570:Nitriles; D010972:Platelet Activating Factor; D014052:Toluidines; C527525:teriflunomide; D004247:DNA; D000077339:Leflunomide