Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy.
Article Details
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Elkahwaji J, Robin MA, Berson A, Tinel M, Letteron P, Labbe G, Beaune P, Elias D, Rougier P, Escudier B, Duvillard P, Pessayre D
Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy.
Biochem Pharmacol. 1999 Apr 15;57(8):951-4.
- PubMed ID
- 10086330 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Aldesleukin Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Aldesleukin Cytochrome P450 3A4 Protein Humans UnknownInhibitorDetails