来氟米特对佐剂性关节炎大鼠腹腔巨噬细胞IL—1，IL—6和TNF—α产生的动态影响

目的:探讨来氟米特(leflunomide,LEF)对佐剂性关节炎大鼠腹腔巨噬细胞IL-1,IL-6和 TNF-α分泌的影响及其抗炎、抗类风湿的可能作用机制.方法:大鼠足跖皮下注射Freund完全佐剂诱导关节炎模型;LEF灌胃后分次获取腹腔巨噬细胞,其培养上清液中IL-1,IL-6和TNF-α活性采用ELISA法或生物法测定.结果:佐剂性关节炎大鼠腹腔巨噬细胞IL-1,IL-6和TNF-α分泌较正常对照组明显升高;LEF对由 LPS诱导产生的 IL-1和 TNF-α有明显的抑制作用,作用产生快;LEF(10,25 mg/kg)在应用21天后对IL-6的分泌也有明显抑制作用.结论:来氟米特具有抑制佐剂性关节炎大鼠腹腔巨噬细胞 IL-1,IL-6和 TNF-α分泌水平的作用.

Dynamic effects of leflunomide on IL-1, IL-6, and TNF-alpha activity produced from peritoneal macrophages in adjuvant arthritis rats

AIM: To investigate the effects of leflunomide (LEF) on modulating interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor- alpha (TNF-alpha) production induced by lipopolysaccharide (LPS) in peritoneal macrophages (PMphi) in adjuvant arthritis rats and elucidate the possible mechanisms of antiinflammatory and antirheumatoid effects of LEF. METHODS: Freund's complete adjuvant was injected in the hind footpad of rats to induce adjuvant arthritis (AA) rat model. The PMphi samples were taken at different time after medication. IL-1, IL-6, and TNF-alpha activities released from PMphi were measured by ELISA method or bioassay method. RESULTS: Production of IL-1, IL-6, and TNF-alpha was increased in the culture supernatant of PMphi in AA model rat. LEF could inhibit LPS-induced release of IL-1 and TNF-alpha from PMphi of the AA rats and the inhibitory effects were extremely rapid. LEF (10, 25 mg/kg) administrated for 21d could inhibit IL-6 release from PMphi in AA rats. CONCLUSION: The antiinflammatory mechanisms of LEF in AA rats might be related to inhibitory level of IL-1, IL-6, and TNF-alpha from PMphi in vivo.