Geiger T, Jagher B, Pignat W, Tscherry B, Wiesenberg I
Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
Agents Actions. 1993;38 Spec No:C69-72. doi: 10.1007/BF01991141.
Using specific cDNA probes, we have investigated drug-induced changes in hepatic mRNA levels of the major acute-phase proteins (APP) fibrinogen, alpha 2-macroglobulin (alpha 2-MG), albumin and alpha 1-acid glycoprotein (alpha 1-AGP) in male Lewis rats with adjuvant arthritis. Test compounds were given orally from day 0 to 20 and hepatic mRNA analysis was performed at day 21. Prednisolone (1, 3, 10 mg/kg), Cyclosporine A (1, 3, 10 mg/kg) and cyclophosphamide (3 mg/kg) dose-dependently normalized hepatic mRNA levels of all four APP. Equipotent anti-inflammatory doses of indomethacin (0.3, 1 mg/kg) significantly downregulated alpha 2-MG mRNA levels but were much less effective in influencing albumin and alpha 1-AGP mRNA levels and even slightly increased hepatic fibrinogen mRNA levels. These results suggest that cytokine over-production, which is thought to be responsible for the acute-phase response in rats with adjuvant arthritis, can be effectively downregulated by immunosuppressive drugs, but is distinctly less affected by the cyclooxygenase inhibitor indomethacin.
利用特异性cDNA探针，我们研究了佐剂性关节炎雄性Lewis大鼠中主要急性期蛋白（APP）纤维蛋白原、α2-巨球蛋白（α2-MG）、白蛋白和α1-酸性糖蛋白（α1-AGP）的肝脏mRNA水平的药物诱导变化。从第0天至第20天口服给予受试化合物，并在第21天进行肝脏mRNA分析。泼尼松龙（1、3、10mg/kg）、环孢素A（1、3、10mg/kg）和环磷酰胺（3mg/kg）均剂量依赖性地使所有四种APP的肝脏mRNA水平恢复正常。等效抗炎剂量的吲哚美辛（0.3、1mg/kg）显著下调α2-MG mRNA水平，但对白蛋白和α1-AGP mRNA水平的影响小得多，甚至略微增加肝脏纤维蛋白原mRNA水平。这些结果表明，细胞因子过度产生被认为是佐剂性关节炎大鼠急性期反应的原因，可被免疫抑制药物有效下调，但受环氧化酶抑制剂吲哚美辛的影响明显较小。
