ALTERATIONS OF HEPATIC DRUG-METABOLISM IN MICE FOLLOWING INFECTION WITH THE MURINE RETROVIRUS LP-BM5

Infection of mice with the murine retrovirus mixture LP-BM5 caused a retrovirai infection with many similarities to human HIV infection, We have reported alterations in hepatic drug metabolism which progressed during the course of this infection. Hexobarbital-induced sleep time increased 1.5-2.2-fold above uninfected controls after 10 to 19 weeks post infection. Inhibition of spectral cytochrome P-450 levels by 25 to 30% was observed between 15 and 17 weeks postinfection, and there were changes in specific microsomal enzyme activities. The microsomal cocaine demethylase activity was reduced by 40%, whereas cytosolic enzyme activities were increased by 1.5-2.0-fold. These alterations may contribute to the altered metabolism of drugs of abuse reported in MAIDS mice. The mechanism for these alterations is not known, although the effects correspond temporally to reported infiltration of the liver with immunoblasts and plasma cells. This suggests a role for the immune system or for mediators released by cells of the immune system which could account for these observations. An understanding of the effects of infection on drug metabolism is important because of their impact on the efficacy and safety of drugs for use in AIDS patients.