Ferrari L, Kremers P, Batt A M, Gielen J E, Siest G
Centre du Médicament, URA CNRS 597, Université de Nancy, France.
Drug Metab Dispos. 1992 May-Jun;20(3):407-12.
The immunomodulator interleukin-1 beta (IL-1) is one of the major inflammatory mediators. In vivo, it has been reported to depress some rat liver cytochromes P-450 (cytochrome P-450). Our aim was to study those effects in vitro, using cultured fetal rat hepatocytes as a model. Testosterone 6 beta-hydroxylase (cytochrome P-450 IIIA family activity) was not depressed by IL-1 treatments, but its induction by dexamethasone was prevented. The effect was time- and dose-dependent. Ethoxyresorufine-O-deethylase (cytochrome P-450 IA1 activity) decreased after IL-1 treatment, and dexamethasone partially prevented this inhibition. Acute phase effects of IL-1 were assayed by albumin and transferrin secretions. The cell's sensitivity to glucocorticoids was determined by tyrosine-aminotransferase activity. Our data demonstrate that IL-1 was able to prevent the glucocorticoid induction of cytochrome P-450 IIIA involving at least two different mechanisms. This is in agreement with the theory suggesting that the induction of CYPIIIA family by glucocorticoids requires the presence of the glucocorticoid receptor and some other regulatory elements. Other cytochrome P-450-dependent activities (IIA1, IIB1/2, and IIC11) were inhibited by IL-1 treatments, depending on dose and time, but some were also protected by dexamethasone.
免疫调节剂白细胞介素 -1β（IL -1）是主要的炎症介质之一。据报道，在体内它会抑制一些大鼠肝脏细胞色素P -450（细胞色素P -450）。我们的目的是使用培养的胎鼠肝细胞作为模型，在体外研究这些作用。睾酮6β -羟化酶（细胞色素P -450 IIIA家族活性）不受IL -1处理的抑制，但地塞米松对其的诱导作用受到阻止。这种作用具有时间和剂量依赖性。IL -1处理后乙氧异羟肟酸 -O -脱乙基酶（细胞色素P -450 IA1活性）降低，地塞米松可部分阻止这种抑制作用。通过白蛋白和转铁蛋白分泌来检测IL -1的急性期作用。通过酪氨酸转氨酶活性来确定细胞对糖皮质激素的敏感性。我们的数据表明，IL -1能够通过至少两种不同机制阻止糖皮质激素对细胞色素P -450 IIIA的诱导。这与以下理论一致，即糖皮质激素对CYPIIIA家族的诱导需要糖皮质激素受体和一些其他调节元件的存在。其他细胞色素P -450依赖性活性（IIA1、IIB1/2和IIC11）受到IL -1处理的抑制，这取决于剂量和时间，但有些也受到地塞米松的保护。
