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.
Poüs
C
C
Département de Pharmacologie, CNRS-URA 595, Hôpital Cochin, Paris, France.
Giroud
J P
JP
Damais
C
C
Raichvarg
D
D
Chauvelot-Moachon
L
L
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D009961:Orosomucoid / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D009961:Orosomucoid; D011506:Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System