Hepatic drug metabolism and immunostimulation

• Published in: Toxicology (Amsterdam) 2000-01, Vol.142 (3), p.173-178
• Main Author: Renton, Kenneth W
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Cytochrome P-450 Enzyme System - metabolism; cytochrome P450; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunity, Innate - immunology; Immunobiology; Infection - enzymology; Infection - immunology; Infection - metabolism; Inflammation - enzymology; Inflammation - immunology; Inflammation - metabolism; Liver - enzymology; Liver - immunology; Liver - metabolism; Liver - pathology; Modulation of the immune response (stimulation, suppression); Oxidoreductases
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(99)00142-0

When host defence mechanisms are stimulated there is a concomitant decrease in cytochrome P450 based drug biotransformation and elimination. This has resulted in a number of clinically important unwanted drug responses in patients with infections or inflammatory responses. The loss in cytochrome P450 is predominantly an effect at the level of the gene expression and the majority of enzyme forms examined to date are involved. Although the effect occurs predominantly in the liver it has been recently shown that inflammatory responses in the brain also cause a loss of the same enzyme forms in that organ.The loss of cytochrome P450 in the brain in response to localised inflammation is accompanied by a similar loss in the liver. The decrease of cytochrome P450 and its dependent drug biotransformation is of concern whenever drugs are used in patients with infections or disease states with an inflammatory component.