Decrease in brain cytochrome P450 enzyme activities during infection and inflammation of the central nervous system

The effect of infection and inflammation of the central nervous system (CNS ) on cytochrome-P450-dependent activities in brain, spinal cord and liver m icrosomes was determined. For this, two models were used: (1) the intracere broventricularly injected lipopolysaccharide (LPS) model and (2) the experi mental auto-immune encephalomyelitis (EAE) model. In the LPS model, aminopy rine N-demethylase (AMND) and ethoxycoumarin O-deethylase (ECOD) activities (both P450 dependent) were significantly decreased (35 and 20%, respective ly) in brain microsomes. In the EAE model, only ECOD activity was significa ntly lower (18%). In the liver, a decrease in total P450, AMND and ECOD act ivities was only observed in the LPS model. In both models, tumour necrosis factor (TNF) was significantly elevated in brain and spinal cord tissues. In serum, TNF was only detectable in the LPS model. It is concluded that an infection or inflammation located in the CNS, which is accompanied by high TNF level, results in a decrease in P450-dependent metabolism not only in the liver but in the brain as well. Copyright (C) 2000 S. Karger AG, Basel.