title: Effects of recombinant human interferon alpha on aryl hydrocarbon hydroxylase activity in cultured human peripheral lymphocytes.
abstract: Interferon and its inducers are known to depress drug biotransformation in vivo by decreasing the levels of cytochrome P-450 (P450) monooxygenase system in the liver. However, very little is known about the effects of interferon on P450 in extrahepatic tissues. In this study we investigated the effects of a recombinant human interferon-alpha (rhIFN-alpha) on aryl hydrocarbon hydroxylase (P450IAI) in cultured human peripheral lymphocytes (HPL). Non-induced and induced (3-methylcholanthrene) mitogen activated lymphocytes were used throughout the study. rhIFN-alpha maximally depressed AHH activity to approximately 58% of control after 24 hrs of incubation in both non-induced and induced lymphocytes. However, after 48 hrs of incubation with rhIFN-alpha, AHH activity had recovered to 86% of control in induced cells and 61% in non-induced cells. rhIFN-alpha had no significant effect on either NADH cytochrome c reductase activity or on viable lymphocyte cell count. This is the first demonstration that rhIFN-alpha can have a direct depressive effect on a P450 dependent monooxygenase system in HPL.
authors.affiliation: Dept of Pharmacology, Faculty of Medicine, National University of Singapore.
authors.forename: S M
authors.initials: SM
authors.lastname: Moochhala
authors.forename: E J
authors.initials: EJ
authors.lastname: Lee
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D009245:NADH Dehydrogenase / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: D007370:Interferon Type I; D011994:Recombinant Proteins; D008748:Methylcholanthrene; D001189:Aryl Hydrocarbon Hydroxylases; D009245:NADH Dehydrogenase