Vol. 29, Issue 7, 1007-1012, July 2001

SHORT COMMUNICATION
Cytochrome P450 Down-Regulation by Serum from Humans with a Viral Infection and from Rabbits with an Inflammatory Reaction

Anne-Marie Bleau, Caroline Fradette, Ayman O. S. El-Kadi, Marie-Claude Côté, and Patrick du Souich

Department of Pharmacology, Faculty of Medicine, University of Montréal, Montréal, Québec, Canada

Serum from humans with an upper respiratory viral infection (HS_URVI) and from rabbits with a turpentine-induced acute inflammatory reaction (RS_TIAR) reduces the activity of hepatic cytochrome P450 (P450) following 4 h of incubation. The aim of the present study was to assess the effect of HS_URVI and RS_TIAR on P450 activity and expression following 24 h of incubation with hepatocytes from control (H_CONT) and rabbits with a TIAR (H_INFLA). RS_TIAR incubated with H_CONT for 24 h reduced P450 content and activity, and CYP3A6 by 45%, without changing CYP1A1 and 1A2; when incubated with H_INFLA, RS_TIAR decreased P450 content and activity without affecting CYP1A1 or 1A2. HS_URVI incubated for 4 h with H_CONT decreased P450 activity without affecting the amounts of CYP1A1, 1A2, or 3A6, although when incubated for 24 h, P450 activity and CYP3A6 amount decreased. HS_URVI incubated with H_INFLA for 4 h reduced P450 content and activity, and incubated for 24 h reduced activity, P450 content, and amount of CYP1A1 and 1A2 proteins. The present study demonstrates that 1) the effect of RS_TIAR and HS_URVI depends upon the susceptibility of the hepatocyte, i.e., H_CONT or primed H_INFLA; 2) P450 down-regulation is preceded by a decrease in P450 activity; 3) the nature of the inflammatory reaction determines the repercussions on P450 activity and expression; and 4) CYP3A6 is more vulnerable than CYP1A1 and 1A2 to the down-regulation provoked by an inflammatory challenge.