Alteration of drug biotransformation by interferon and host defence mechanism.
It has been demonstrated that the liver loses its capacity to metabolise and eliminate drugs during viral infection or during the operation of host defence mechanisms. This loss in drug metabolism is due to the loss of the cytochrome P-450 component of the mixed function oxidase (the enzyme system primarily responsible for the oxidation of drugs, carcinogens and certain classes of endogenous substances such as steroids, fatty acids and prostaglandins). At present we have identified interferon and factors such as interleukin-1, interleukin-6 and tumour necrosis factor, released from Kupffer cells, as major mediators of the loss. The depression that occurs during viral infection is mediated via the production of interferon. This action of interferon requires the synthesis of an intermediate/s yet to be identified. The molecular mechanism for the decrease in cytochrome P-450 mediated drug metabolism during episodes of viral infections is caused by an interferon-mediated loss in mRNA and subsequent cytochrome P-450 synthesis in the liver.
Moochhala
S M
SM
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D007109:Immunity; D007239:Infections / Q000378:metabolism; D007369:Interferon Inducers / Q000494:pharmacology; D007372:Interferons / Q000502:physiology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism
D000276:Adjuvants, Immunologic; D007369:Interferon Inducers; D004364:Pharmaceutical Preparations; D007372:Interferons; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases