DIFFERENTIAL EFFECT OF INTERLEUKIN-1-ALPHA ON RAT HEPATIC CYTOCHROME-P450 MONOOXYGENASES

Administration of recombinant human interleukin-1 alpha to adult male rats caused a significant reduction in the levels of hepatic cytochrom e P450 and P450 reductase activity at 24 h after the treatment. The mR NAs for cytochrome P450 1A2 and 2E1 were reduced more than 70% at 12 h after administration of interleukin-1 alpha and remained decreased ev en after 48 h. By contrast, cytochrome P450 2C11 mRNA was reduced only by 30% at 12 h after the treatment and returned to the control levels by 48 h, suggesting that interleukin-1 alpha has a differential effec t on the expression of P450 mRNAs. Aniline hydroxylase, benzphetamine N-demethylase and 7-ethoxycoumarin O-deethylase activities were signif icantly decreased at 24 h after interleukin-1 alpha treatment. The pro teins for cytochrome P450 1A2 and 2E1 were reduced by about 50% at 24 h after interleukin-1 alpha treatment.