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 systems 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-α) on aryl hydrocarbon hydroxylase (P450IAI) in cultured human peripheral lymphocytes (HPL). Non-induced and induced (3-methylcholantherene) mitogen activated lymphocytes were used throughout the study. rhIFN-α 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-α, AHH activity had recovered to 86% of control in induced cells and 61% in non-induced cells. rhIFN-α had no significant effect on either NADH cytochrome c reductase activity or on viable lymphocyte cell count. This is the first demonstration that rhIFN-α can have a direct depressive effect on a P450 dependent monooxygenase system in HPL.