Effect of recombinant human interleukin-1 beta and tumor necrosis factor alpha on liver cytochrome P-450 and serum alpha-1-acid glycoprotein concentrations in the rat.

Two hepatocyte-related effects of recombinant human interleukin-1 beta and tumor necrosis factor alpha alone or in association were tested following iv administration to Fischer 344 rats. Within 24 hr, both monokines induced a dose-dependent decrease in cytochrome P-450 levels, whereas serum alpha-1-acid glycoprotein concentrations were strongly increased. The largest variation of both parameters was observed using a combination of the two monokines. Dexamethasone, which possesses anti-interleukin-1 properties and is known to stimulate alpha-1-acid glycoprotein synthesis in rats, also depressed cytochrome P-450 levels, suggesting that alpha-1-acid glycoprotein might mediate the monokine-related inhibition of drug metabolism. Nevertheless, at the lowest doses of monokines tested, only cytochrome P-450 levels were modified. The transfer of a post-dexamethasone serum to normal rats did not change cytochrome P-450 levels.