Peterson T C, Renton K W
Immunopharmacology. 1986 Feb;11(1):21-8. doi: 10.1016/0162-3109(86)90061-5.
Cytochrome P-450-mediated drug biotransformation is depressed by many immune stimulants. We have shown that such depression caused by the immune stimulant dextran sulfate is mediated by Kupffer cells. The purpose of this study is to determine if other cells of the immune system or a cellular product such as interferon are involved in the depressive action of dextran sulfate on drug metabolism. Plasma samples taken from mice treated with dextran sulfate contained no detectable interferon, yet hepatic cytochrome P-450 was significantly depressed, suggesting that interferon did not mediate the depression of drug metabolism by dextran sulfate. Administration of cyclophosphamide or antilymphocyte serum to mice prior to dextran sulfate to markedly decrease lymphocyte populations did not prevent the depressive actions of dextran sulfate on cytochrome P-450, suggesting that the lymphocyte population was not involved in the dextran sulfate mediated depression. Preincubation of dextran sulfate with peritoneal macrophages prior to incubation with hepatocytes significantly depressed hepatocyte cytochrome P-450 content, while dextran sulfate alone had no direct effect on hepatocyte cytochrome P-450 content. These results further support the hypothesis that macrophages play a major role in the depression of cytochrome P-450 by dextran sulfate.
细胞色素P - 450介导的药物生物转化受到多种免疫刺激剂的抑制。我们已经表明，免疫刺激剂硫酸葡聚糖引起的这种抑制作用是由库普弗细胞介导的。本研究的目的是确定免疫系统的其他细胞或诸如干扰素之类的细胞产物是否参与硫酸葡聚糖对药物代谢的抑制作用。从用硫酸葡聚糖处理的小鼠采集的血浆样本中未检测到干扰素，但肝细胞色素P - 450显著降低，这表明干扰素并未介导硫酸葡聚糖对药物代谢的抑制作用。在给予硫酸葡聚糖之前给小鼠施用环磷酰胺或抗淋巴细胞血清以显著减少淋巴细胞数量，并不能阻止硫酸葡聚糖对细胞色素P - 450的抑制作用，这表明淋巴细胞群体不参与硫酸葡聚糖介导的抑制作用。在与肝细胞共同孵育之前，先将硫酸葡聚糖与腹腔巨噬细胞预孵育，可显著降低肝细胞色素P - 450含量，而单独的硫酸葡聚糖对肝细胞色素P - 450含量没有直接影响。这些结果进一步支持了巨噬细胞在硫酸葡聚糖对细胞色素P - 450的抑制作用中起主要作用这一假说。
