EFFECTS OF LEFLUNOMIDE (HWA-486) ON EXPRESSION OF LYMPHOCYTE-ACTIVATION MARKERS

Leflunomide (HWA 486), an isoxazol derivative, has been shown to be ve ry effective in combating autoimmune diseases and transplantation reje ction in a great number of animal models. The main metabolite of leflu nomide, A77 1726, is a potent antiproliferative compound. To further e lucidate this effect, lymphocytes of healthy human donors were culture d for 24, 48 or 72h in the presence of PHA or immobilized anti-CD3 ant ibody. A77 1726 was added at concentrations between 10 and 100 muM. Fl ow cytometric evaluation of early activation or proliferation markers (IL-2 and transferrin receptors, respectively) showed that their expre ssion was inhibited in a dose-dependent manner by A77 1726. Together w ith previous data, these experiments indicate that leflunomide not onl y inhibits the expansion of already proliferating lymphocytes, but als o impairs PHA and anti-CD3 antibody triggered activation of quiescent cells. Thus, this compound may exert its effects through influencing t wo important aspects of an immune response, that is, activation and pr oliferation of lymphocytes.