Effects of leflunomide (HWA 486) on expression of lymphocyte activation markers

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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.