来氟米特对佐剂性关节炎大鼠腹腔巨噬细胞产生的白细胞介素-1、白细胞介素-6和肿瘤坏死因子-α活性的动态影响。
Dynamic effects of leflunomide on IL-1, IL-6, and TNF-alpha activity produced from peritoneal macrophages in adjuvant arthritis rats.
作者信息
Li Wei-Dong, Ran Guo-Xia, Teng Hui-Ling, Lin Zhi-Bin
机构信息
Department of Pharmacology, Health Science Center of Peking University, Beijing 100083, China.
出版信息
Acta Pharmacol Sin. 2002 Aug;23(8):752-6.
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.
目的
研究来氟米特（LEF）对佐剂性关节炎大鼠腹腔巨噬细胞（PMphi）中脂多糖（LPS）诱导的白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）产生的调节作用，并阐明LEF抗炎和抗类风湿作用的可能机制。
方法
将弗氏完全佐剂注射到大鼠后足垫以诱导佐剂性关节炎（AA）大鼠模型。在给药后的不同时间采集PMphi样本。采用ELISA法或生物测定法检测PMphi释放的IL-1、IL-6和TNF-α活性。
结果
AA模型大鼠PMphi培养上清中IL-1、IL-6和TNF-α的产生增加。LEF可抑制AA大鼠PMphi中LPS诱导的IL-1和TNF-α释放，且抑制作用极快。连续21天给予LEF（10、25mg/kg）可抑制AA大鼠PMphi中IL-6的释放。
结论
LEF在AA大鼠中的抗炎机制可能与体内抑制PMphi产生IL-1、IL-6和TNF-α的水平有关。
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