Zielinski T, Müller H J, Bartlett R R
Department of Immunology, University of Mainz, FRG.
Agents Actions. 1993;38 Spec No:C80-2. doi: 10.1007/BF01991144.
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 effect, lymphocytes of healthy human donors were cultured for 24, 48 or 72 h in the presence of PHA or immobilized anti-CD3 antibody. A77 1726 was added at concentrations between 10 and 100 microM. 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.
来氟米特（HWA 486），一种异恶唑衍生物，已被证明在大量动物模型中对抗自身免疫性疾病和移植排斥反应非常有效。来氟米特的主要代谢产物A77 1726是一种有效的抗增殖化合物。为了进一步阐明这种作用，将健康人类供体的淋巴细胞在PHA或固定化抗CD3抗体存在下培养24、48或72小时。加入浓度为10至100微摩尔的A77 1726。对早期激活或增殖标志物（分别为IL-2和转铁蛋白受体）的流式细胞术评估表明，它们的表达受到A77 1726的剂量依赖性抑制。与先前的数据一起，这些实验表明来氟米特不仅抑制已增殖淋巴细胞的扩增，而且还损害PHA和抗CD3抗体触发的静止细胞激活。因此，该化合物可能通过影响免疫反应的两个重要方面，即淋巴细胞的激活和增殖来发挥其作用。
