Decrease in hepatic cytochrome P450 after interleukin-2 Immunotherapy

Interleukin-2 (IL-2) has been shown to decrease cytochrome P450 (CYP) mRNAs and proteins in cultured rat hepatocytes, and IL-2 administration decrease s CYPs in rats. Although high doses of IL-2 are administered to cancer pati ents, the effect on human CYPs has not yet been determined. Patients with h epatic metastases from colon or rectum carcinomas were randomly allocated t o 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 conse rvation 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/m(2), compared to 7 pat ients who did not receive IL-2. In contrast, in 6 patients receiving daily doses of 9 or 12 . 106 IL-2 units/m(2), 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%, methoxyre sorufin O-demethylation by 62%, and erythromycin N-demethylation by 50%. Th ese observations suggest that high doses of IL-2 may decrease total CYP and monooxygenase activities in man. BIOCHEM PHARMACOL 57;8:951-954, 1999. (C) 1999 Elsevier Science Inc.