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Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy.

Abstract：

: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.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Elkahwaji J,Robin MA,Berson A,Tinel M,Lettéron P,Labbe G,Beaune P,Elias D,Rougier P,Escudier B,Duvillard P,Pessayre D

doi

10.1016/s0006-2952(98)00372-4

subject

Has Abstract

pub_date

1999-04-15 00:00:00

pages

951-4

issue

8

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(98)00372-4

journal_volume

57

pub_type

临床试验,杂志文章,随机对照试验

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