Poüs C, Giroud J P, Damais C, Raichvarg D, Chauvelot-Moachon L
Département de Pharmacologie, CNRS-URA 595, Hôpital Cochin, Paris, France.
Drug Metab Dispos. 1990 Jul-Aug;18(4):467-70.
Two hepatocyte-related effects of recombinant human interleukin-1 beta and tumor necrosis factor alpha alone or in association were tested following iv administration to Fischer 344 rats. Within 24 hr, both monokines induced a dose-dependent decrease in cytochrome P-450 levels, whereas serum alpha-1-acid glycoprotein concentrations were strongly increased. The largest variation of both parameters was observed using a combination of the two monokines. Dexamethasone, which possesses anti-interleukin-1 properties and is known to stimulate alpha-1-acid glycoprotein synthesis in rats, also depressed cytochrome P-450 levels, suggesting that alpha-1-acid glycoprotein might mediate the monokine-related inhibition of drug metabolism. Nevertheless, at the lowest doses of monokines tested, only cytochrome P-450 levels were modified. The transfer of a post-dexamethasone serum to normal rats did not change cytochrome P-450 levels.
在对Fischer 344大鼠静脉注射后，测试了重组人白细胞介素-1β和肿瘤坏死因子α单独或联合使用时的两种肝细胞相关效应。在24小时内，两种单核因子均诱导细胞色素P-450水平呈剂量依赖性下降，而血清α-1-酸性糖蛋白浓度则显著升高。使用两种单核因子的组合观察到这两个参数的最大变化。地塞米松具有抗白细胞介素-1特性，并且已知能刺激大鼠体内α-1-酸性糖蛋白的合成，它也会降低细胞色素P-450水平，这表明α-1-酸性糖蛋白可能介导单核因子相关的药物代谢抑制。然而，在测试的最低剂量单核因子下，只有细胞色素P-450水平发生了改变。将地塞米松注射后的血清转移到正常大鼠体内并没有改变细胞色素P-450水平。
