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首页> 外文期刊>Biochemical Pharmacology >Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy.
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Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy.

机译：白介素2免疫治疗后肝细胞色素P450的减少。

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摘要

Interleukin-2 (IL-2) has been shown to decrease cytochrome P450 (CYP) mRNAs and proteins in cultured rat hepatocytes, and IL-2 administration decreases CYPs in rats. Although high doses of IL-2 are administered to cancer patients, the effect on human CYPs has not yet been determined. Patients with hepatic metastases from colon or rectum carcinomas were randomly allocated to various daily doses of human recombinant IL-2 (from 0 to 12.10(6) units/m(2)). IL-2 was infused from day 7 to day 3 before hepatectomy and the conservation of a non-tumorous liver fragment in liquid nitrogen. Hepatic CYPs and monooxygenase activities were not significantly decreased in 5 patients receiving daily doses of 3 or 6 10(6) IL-2 units/m2, compared to 7 patients who did not receive IL-2. In contrast, in 6 patients receiving daily doses of 9 or 12 x 10(6) IL-2 units/m2, the mean values for immunoreactive CYP1A2, CYP2C, CYP2E1, and CYP3A4 were 37, 45, 60 and 39%, respectively, of those in controls; total CYP was significantly decreased by 34%, methoxyresorufin O-demethylation by 62%, and erythromycin N-demethylation by 50%. These observations suggest that high doses of IL-2 may decrease total CYP and monooxygenase activities in man.
机译：已显示白介素2（IL-2）可以降低培养的大鼠肝细胞中的细胞色素P450（CYP）mRNA和蛋白，而IL-2的给药可以降低大鼠中的CYP。尽管向癌症患者施用高剂量的IL-2，但尚未确定对人CYP的影响。从结肠癌或直肠癌有肝转移的患者被随机分配到各种日剂量的人类重组IL-2（从0到12.10（6）单位/ m（2））。从肝切除术的第7天到第3天输注IL-2，并在液氮中保存非肿瘤性肝碎片。每天接受3或6 10（6）IL-2单位/ m2剂量的5例患者的肝CYP和单加氧酶活性没有明显降低，而未接受IL-2的7例患者的肝CYP和单加氧酶活性没有明显降低。相比之下，在6名每天接受9或12 x 10（6）IL-2单位/ m2剂量的患者中，免疫反应性CYP1A2，CYP2C，CYP2E1和CYP3A4的平均值分别为37％，45％，60％和39％。在控制者中;总CYP显着降低了34％，甲氧基间苯二酚的O-去甲基化降低了62％，红霉素N-去甲基化降低了50％。这些观察结果表明，高剂量的IL-2可能会降低人体的总CYP和单加氧酶活性。

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