Effect Of Recombinant Tumor Necrosis Factor On Cyp450 System

Ghezzi et al. (35) studied the effect of recombinant TNF on liver CYP450 and related drug metabolism enzymes in male CD1 mice. Treatment of mice with rTNF caused a marked depression of activities of CYP450, ethoxycoumarin deethylase, and arylhydrocarbon hydroxylase in the liver and other organs such as intestine, lung, and adrenal. This effect was maximal 24 to 48 hours after treatment and was dose dependent. Depression of liver drug-metabolizing enzymes was also observed in the endotoxin-resistant C3H/HeJ strain of mice, thus ruling out that this effect may be due to minor endotoxin contamination of rTNF. These data indicate that depression of liver drug metabolism might be an important side effect of rTNF when given with drugs that are metabolized by CYP450 system.

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