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Journal 'Cytokines & inflammation', 2004, No. 1

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Original Articles

Number 1'2004

EFFECT OF RECOMBINANT IL-1B ON HEPATIC AND RENAL CYTOCHROME P450-DEPENDENT MONOOXYGENASES. ASSOCIATION BETWEEN SPECIFIC AND NEUROENDOCRINE EFFECTS

A.T. Akhmatov, S.V. Sibiryak, A.S. Simbirtsev, D.S. Sibiryak

In experiments on non-inbred male rats human recombinant IL-1b (Betaleukin) (6.5 - 105 IU/kg, single dose, intraperitoneally) stimulated granulocytopoesis, decreased mitotic activity of splenocytes and thymocytes, induced thymocyte apoptosis, increased corticosterone plasma level and changed hepatic and renal cytochrome P450-dependent monooxygenase activity in an isoenzyme-specific and tissue-specific manner. Betaleukin suppressed hepatic CYP1A1/2-dependent ethoxyresorufine O-deethylation, CYP2C-dependent dibenzylfluorescein debenzylase activity, CYP2E1-dependent p-nitrophenol hydroxylation and renal CYP1A1/2-dependent ethoxyresorufine deethylation. However the CYP3A-specific erythromycin N-demethylation was induced both in the liver and kidneys. Cytochromes P450 CYP3A subfamily, the major steroid-inducible cytochromes, are responsible for corticosteroid 6b-hydroxylation and "terminal" biotransformation. Thus, increased CYP3A-dependent monooxygenase activity may be due to the increased corticosteron plasma level and reflects the mechanism of the self-regulation during the IL-1b-induced "immune stress". (Cytokines and Inflammation. 2004. Vol. 3, N1. P. 32-38.)

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