Inflammation Research

, Volume 44, Issue 8, pp 317–322

Leflunomide interferes with pyrimidine nucleotide biosynthesis

Authors

  • H. M. Cherwinski
    • The Institute of ImmunologySyntex Discovery Research S3-6
  • N. Byars
    • The Institute of ImmunologySyntex Discovery Research S3-6
  • S. J. Ballaron
    • The Institute of ImmunologySyntex Discovery Research S3-6
  • G. M. Nakano
    • The Institute of ImmunologySyntex Discovery Research S3-6
  • J. M. Young
    • The Institute of ImmunologySyntex Discovery Research S3-6
  • J. T. Ransom
    • The Institute of ImmunologySyntex Discovery Research S3-6
Original Research Papers

DOI: 10.1007/BF01796261

Cite this article as:
Cherwinski, H.M., Byars, N., Ballaron, S.J. et al. Inflamm Res (1995) 44: 317. doi:10.1007/BF01796261

Abstract

Leflunomide is an anti-inflammatory and immunosuppressive agent which blocks proliferation of transformed cells and mitogen stimulated normal lymphocytes but does not block T cell signalling mechanisms at antiproliferative concentrations. These properties are consistent with a mechanism involving interference with nucleotide metabolism. Leflunomide had anti-proliferative activity against all cells tested here. The anti-proliferative activities could be reversed by addition of uridine or cytidine to the cultures although some species and cellular differences were observed. Purine nucleosides had no effect. Measurements of nucleotide pools in a human T cell line and mitogen stimulated rat spleen cells treated with leflunomide showed that leflunomide preferentially reduces pyrimidine nucleotide levels. These results indicate that inhibition of pyrimidine biosynthesis is responsible for the anti-proliferative effects of leflunomide.

Key words

LeflunomidePurine nucleotideDihydro-orotate dehydrogenaseDHODT cell
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Copyright information

© Birkhäuser Verlag 1995