The effects of interleukin 2 and alpha-interferon administration on hepatic drug metabolism in mice.
We have administered the cytokines interleukin 2 (IL-2), alpha-interferon (IFN-alpha), and gamma-interferon (IFN-gamma) to mice and measured the alterations in hepatic drug-metabolizing enzyme activities. For comparative purposes and to understand the mechanism of diphtheria and tetanus toxoids and pertussis (DTP) vaccine-induced inhibition of drug metabolism, we also studied the effects of vaccine administration in mice. The administration of IL-2 alone or in combination with IFN-alpha or IFN-gamma causes dose-dependent increases in hexobarbital-induced sleep times. These increases correlate well with the inhibition of specific microsomal mixed-function oxidase activities. Sublethally irradiated mice and athymic nude mice receiving injections of IL-2 or IL-2 plus IFN-alpha do not show the inhibition of drug metabolism seen in normal mice. However, the inhibition of drug metabolism in DTP vaccine-treated mice was similar in all three groups. These observations indicate a possible role for immune cells (probably T-lymphocytes) in the inhibition of drug metabolism caused by administration of these cytokines, which is different from the inhibition of drug metabolism caused by DTP vaccine.
Ansher
S S
SS
Laboratory of Bacterial Toxins, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
Puri
R K
RK
Thompson
W C
WC
Habig
W H
WH
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000494:pharmacology; D005260:Female; D006591:Hexobarbital / Q000378:metabolism; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008862:Microsomes, Liver / Q000201:enzymology; D011994:Recombinant Proteins
D015721:Diphtheria-Tetanus-Pertussis Vaccine; D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma; D006591:Hexobarbital