Leflunomide inhibits cytokine-induced DNA synthesis of rabbit synovial cells in culture

• Published in: Zhōngguó yàolĭ xuébào Vol. 15; no. 3; pp. 223 - 226
• Main Authors: Ju, D W, Zheng, Q Y, Wang, H B, Fang, J
• Format: Journal Article
• Language: English
• Published: Beijing Science Press 01.05.1994
• Subjects: Aniline Compounds - pharmacology; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cell Division - drug effects; Cells, Cultured; Cytokines - antagonists & inhibitors; DNA - biosynthesis; Hydroxybutyrates - pharmacology; Isoxazoles - pharmacology; Medical sciences; Pharmacology. Drug treatments; Rabbits; Synovial Membrane - cytology; Synovial Membrane - metabolism; Cell proliferation; Cell culture; Cytokine; Rabbit; DNA synthesis; Lagomorpha; In vitro; Vertebrata; Mammalia; Synovial membrane; Animal; Antirheumatic agent; Mechanism of action
• ISSN: 0253-9756

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.