Thoss K, Henzgen S, Petrow P K, Katenkamp D, Brauer R
Institute of Pathology, Friedrich Schiller University, Jena, Germany.
Inflamm Res. 1996 Feb;45(2):103-7. doi: 10.1007/BF02265123.
The effects of the new immunomodulating isoxazol derivative leflunomide, in comparison with cyclosporin A, on established antigen-induced arthritis in rats as well as serum antibody levels were determined. When treatment with leflunomide, at concentrations from 2.5 to 10 mg/kg/d, was started on day 3 of arthritis, the acute and chronic phases of arthritis were effectively inhibited. This was demonstrated by decreased joint swelling and reduced histopathological arthritis score at the end of experiment (day 26). Furthermore, the treatment resulted in a significantly reduced level of serum antibodies to the matrix components collagen type I, type II and proteoglycans. Neither leflunomide nor cyclosporin A, at doses of 1 mg/kg/d, had an effect on the severity of arthritis and antibody levels. However, when both drugs were used together, at these non-effective doses, the histopathological score of chronic arthritis was significantly reduced. The results of our experiments demonstrate that leflunomide has a strong suppressive effect on both acute and chronic phases of antigen-induced arthritis and formation of autoantibodies in rats. Furthermore, orally administered doses of leflunomide were as effective as doses of cyclosporin A given intraperitoneally. The combination of sub-effective doses of leflunomide and cyclosporin A resulted in significant inhibition of chronic arthritis.
研究了新型免疫调节异恶唑衍生物来氟米特与环孢素A相比，对大鼠已建立的抗原诱导性关节炎以及血清抗体水平的影响。当在关节炎第3天开始用浓度为2.5至10mg/kg/d的来氟米特治疗时，关节炎的急性期和慢性期均得到有效抑制。实验结束时（第26天）关节肿胀减轻和组织病理学关节炎评分降低证明了这一点。此外，该治疗导致血清中针对基质成分I型胶原、II型胶原和蛋白聚糖的抗体水平显著降低。剂量为1mg/kg/d的来氟米特和环孢素A对关节炎严重程度和抗体水平均无影响。然而，当以这些无效剂量联合使用这两种药物时，慢性关节炎的组织病理学评分显著降低。我们的实验结果表明，来氟米特对大鼠抗原诱导性关节炎的急性期和慢性期以及自身抗体的形成均有强烈的抑制作用。此外，口服来氟米特的剂量与腹腔注射环孢素A的剂量效果相同。来氟米特和环孢素A的亚有效剂量联合使用可显著抑制慢性关节炎。
