Effects of recombinant human interferon alpha on aryl hydrocarbon hydroxylase activity in cultured human peripheral lymphocytes

• Published in: Life sciences (1973) Vol. 48; no. 18; p. 1715
• Main Authors: Moochhala, S M, Lee, E J
• Format: Journal Article
• Language: English
• Published: Netherlands 1991
• Subjects: Adult; Aryl Hydrocarbon Hydroxylases - metabolism; Cells, Cultured; Humans; Interferon Type I - pharmacology; Kinetics; Lymphocyte Activation; Lymphocytes - drug effects; Lymphocytes - enzymology; Lymphocytes - immunology; Male; Methylcholanthrene - pharmacology; NADH Dehydrogenase - metabolism; Recombinant Proteins
• ISSN: 0024-3205
• DOI: 10.1016/0024-3205(91)90207-R

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.