Abstract
Leflunomide (HWA 486), an isoxazol derivative, has been shown to be very effective in combating autoimmune diseases and transplantation rejection in a great number of animal models. The main metabolite of leflunomide, A77 1726, is a potent antiproliferative compound. To further elucidate this affect, lymphocytes of healthy human donors were cultured for 24, 48 or 72h in the presence of PHA or immobilized anti-CD3 antibody. A77 1726 was added at concentrations between 10 and 100 μM. Flow cytometric evaluation of early activation or proliferation markers (IL-2 and transferrin receptors, respectively) showed that their expression was inhibited in a dose-dependent manner by A77 1726. Together with previous data, these experiments indicate that leflunomide not only inhibits the expansion of already proliferating lymphocytes, but also impairs PHA and anti-CD3 antibody triggered activation of quiescent cells. Thus, this compound may exert its effects through influencing two important aspects of an immune response, that is, activation and proliferation of lymphocytes.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
R. R. Bartlett, M. Dimitrijevic, T. Mattar, T. Zielinski, T. Germann, E. Rüde, G. H. Thoenes, C. C. A. Küchle, H.-U. Schorlemmer, E. Bremer, A. Finnegan and R. Scleyerbach,Leflunomide (HWA 486), a novel immunomodulating compound for the treatment of autoimmune disorders and reactions leading to transplantation rejection. Agents and Actions32, 10–21 (1991).
T. T. Glant, K. Mikecz, R. R. Bartlett, F. Deak, E. Thonar, J. Williams, T. Mattar, K. Kuettner and R. Schleyerbach,Immunomodulation of proteoglycan-induced progressive polyarthritis by leflunomide Immunopharmacol.23, 105–116 (1992).
T. A. Waldmann,The structure, function and expression of interleukin-2 receptors on normal and malignant T cells. Science232, 727–732 (1986).
L. M. Neckers,Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc. Natl. Acad. Sci. USA90, 3494–3498 (1983).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zielinski, T., Müller, H.J. & Bartlett, R.R. Effects of leflunomide (HWA 486) on expression of lymphocyte activation markers. Agents and Actions 38 (Suppl 2), C80–C82 (1993). https://doi.org/10.1007/BF01991144
Issue Date:
DOI: https://doi.org/10.1007/BF01991144