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The Effects of Interleukin 2 and -Interferon Administration on Hepatic Drug Metabolism in Mice

Laboratory of Bacterial Toxins [S. S. A., W. C. T., W. H. H.], Divisions of Bacterial Products and Cytokine Biology [R. K. P.], Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

We have administered the cytokines interleukin 2 (IL-2), -interferon (IFN-), and -interferon (IFN-) 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- or IFN- 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- 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.

¹ To whom requests for reprints should be addressed, at Laboratory of Bacterial Toxins, Center for Biologics Evaluation and Research, Building 29, Room 528, Food and Drug Administration, 8800 Rockville Pike, Bethesda, MD 20892.

Received 7/ 3/91. Accepted 11/ 1/91.

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