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Journal 'Cytokines & inflammation', 2003, No. 2

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Number 2'2003

CYTOKINES AS CYTOCHROME P450-DEPENDENT MONOOXYGENASES REGULATORS. THEORETICAL AND APPLIED ASPECTS

S.V. Sibiryak

The cytochrome P450-dependent monoxygenases are responsible for the oxidative biotransformation of numerous foreign chemicals (xenobiotics), uptaken by a living organism, as well as endogenous lipophilic bioregulator molecules (endobiotics) including certain steroids, arachidonates, retinoides. Depression of cytochrome P450 level and corresponding monoxygenases' activities in liver and other tissues is usually revealed during bacterial and viral infections, immunization with various antigens and in the case of pharmacological immunostimulation. The depressive effect is mediated via cytokines and was ascribed to IFNa, IFNb, IFNg, IL-1 Ё TNF, IL-6, IL-11, IL-2. Cytokines down-regulate gene transcription and mRNA level of different cytochrome P450 isoenzymes; suppression the cytochrome P450 protein synthesis at the post-transcriptional level was also reported. The cytokine-dependent modulation of cytochrome P450 function is responsible for the adaptation of xenobiotics and endobiotics biotransformation in case of immune activation ("immune stress"). On the one hand, this mechanism is necessary for protection against the uncontrolled cytochrome P450 induction which is extremly dangerous for the organism and for maintenance of the oxidative balance. On the other hand, by this way cytokines regulate the level of lipophilic signalling molecules and rate of their neogenesis. From clinical point of view, the changes in different drugs pharmacodynamics and toxicity in patients receiving recombinant cytokines' treatment is important. This fact is related to the depression of hepatic oxidases.

Keywords: cytochrome P450-dependent monooxygenases, cytokines, homeostasis.

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