INTERLEUKIN-1-BETA ANTAGONIZES PHENOBARBITAL INDUCTION OF SEVERAL MAJOR CYTOCHROMES P450 IN ADULT-RAT HEPATOCYTES IN PRIMARY CULTURE

We have investigated the effects of interleukin (IL)-1 beta and IL6 on expression and phenobarbital (PB) induction of ethoxyresorufin O-deet hylase (EROD) and pentoxyresorufin O-deethylase (PROD) activities, as well as on mRNA levels of cytochromes P450 (CYP) 1A, 2B, 2C, 2E and 3A , in rat hepatocytes in primary culture. IL6 slightly antagonized PB-i nduced PROD activity. Strikingly, IL1 beta strongly inhibited basal ER OD and PROD activities, and fully blocked their induction by PB in a d ose-dependent fashion. Furthermore IL1 beta completely suppressed PB i nduction of all CYP mRNAs analyzed. Our results demonstrate that IL1 b eta can suppress basal CYP activities, as well as PB-inducible express ion of five CYP mRNAs in rat hepatocytes in primary culture.