The Effects of Human Recombinant Il-1β on Rat Hepatic and Renal Cytochrome P450-Mediated Monooxygenase Activities

The effects of human recombinant IL-1β (BETALEUKIN) (6 × 10 4 – 6 × 10 6 U/Kg, intraperitoneally, single dose) on liver histology and cytochrome P450 (CYP450s)-mediated hepatic and renal monooxygenase activities were studied in adult male rats. rIL-1β (24 h after treatment) caused proinflammatory changes in liver histology in a dose-dependent manner which were the focal areas of hepatocellular dystrophy, perivascular polymorphonuclear cells infiltration, erythrocytes diapedesis, Kupffer cells and hepatocytes proliferation. Treatment with the rIL-1β caused the dose-dependent depression of the hepatic and renal CYP1A1/2-mediated ethoxyresorufin- O -deethylation (EROD), however showed variable effects of the CYP2E1-mediated p -nitrophenol hydroxylation (PNPH) and CYP3A-mediated erythromycin- N -demethylation (ERND). The hepatic PNPH activity was suppressed by the rIL-1β in doses of 6 × 10 6 U/kg and 6 × 10 4 U/Kg, and renal p -nitrophenol hydroxylation was suppressed only in a dose of 3 × 10 5 U/Kg. The hepatic ERND activity was up regulated after the rIL-1β treatment (3 × 10 5 U/Kg – 6 × 10 5 ), and the renal ERND activity was suppressed in a dose of 3 × 10 5 U/Kg. It is important that the possible effects of cytokines on individual CYP450s are characterized, so that concurrent drug therapy can be managed efficiently and pharmacokinetic interaction be avoided