ABSTRACT
Induction of gamma (Type II) interferon results in depression of the cytochrome P-450 system of mice. The gamma interferon is induced by sensitization of mice with Mycobacterium bovis strain BCG followed by challenge with tuberculin. The degree of depression of the cytochrome P-450 system correlates with the levels of interferon induced. passive transfer of exogenous gamma interferon also results in depression of the murine cytochrome P-450 system. In the present study the metabolism of diphenylhydantoin, a drug metabolized by the cytochrome P-450 system, was examined in mice in which gamma interferon was induced. The metabolism of diphenylhydantoin was severely inhibited in mice in which interferon was induced, and the level of inhibition correlated with the liter of gamma interferon induced. Passive transfer of gamma interferon also depressed the metabolism of diphenylhydantoin by the murine cytochrome P-450 system.
Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Interferons/metabolism , Phenytoin/metabolism , Animals , BCG Vaccine/pharmacology , Female , Interferons/pharmacology , Mice , Microsomes, Liver/metabolism , Tuberculin/pharmacologyABSTRACT
The induction and passive transfer of interferons have been shown to depress the level of cytochrome P-450 drug metabolism system of liver microsomes. Inducers of alpha or beta (Type I) interferons, such as Tilorone-HCl, statalon, mengovirus and others, suppressed the cytochrome P-450 system of rats or mice after administration. Induction of gamma (Type II) interferon also resulted in depression of the cytochrome P-450 system of mice. The gamma interferon was induced by sensitization of mice with Mycobacterium bovis strain BCG followed by challenge with tuberculin. The degree of depression of the cytochrome P-450 system correlated with the levels of interferon induced. In addition, passive transfer of exogenous gamma interferon also resulted in depression of the murine cytochrome-450 system. The metabolism of diphenylhydantoin, a drug metabolized by cytochrome-450, was examined in mice in which gamma interferon was induced. The metabolism of diphenylhydanoin was severely inhibited in mice which interferon was induced, and the level of inhibition correlated with the titer of gamma interferon induced. Passive transfer of gamma interferon also depressed the metabolism of diphenylhydantoin by murine cytochrome P-450.
Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Interferon-gamma/biosynthesis , Pharmaceutical Preparations/metabolism , Aminopyrine N-Demethylase/metabolism , Animals , Cytochrome b Group/metabolism , Cytochromes b5 , Mice , Microsomes, Liver/drug effects , Microsomes, Liver/enzymology , Mycobacterium bovis/immunology , Phenytoin/metabolismABSTRACT
Induction of type II interferon by sensitization of mice with Mycobacterium tuberculosis strain BCG and challenge with tuberculin resulted in a depression of the cytochrome P-450 drug metabolism system of the liver. The degree of depression was significantly greater than in mice that were only sensitized to BCG. Cytochrome b5 levels were not affected. In addition, the level of the depression of the cytochrome P-450 system correlated with the levels of type II interferon induced. Passive transfer of exogenous type II interferon preparations also significantly depressed the cytochrome P-450 system. Passive transfer of mock interferon or of normal serum had no effect.
