Interleukin-1 beta antagonizes phenobarbital induction of several major cytochromes P450 in adult rat hepatocytes in primary culture

FEBS Lett. 1995 Jun 12;366(2-3):159-64. doi: 10.1016/0014-5793(95)00513-9.


We have investigated the effects of interleukin (IL)-1 beta and IL6 on expression and phenobarbital (PB) induction of ethoxyresorufin O-deethylase (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-induced PROD activity. Strikingly, IL1 beta strongly inhibited basal EROD and PROD activities, and fully blocked their induction by PB in a dose-dependent fashion. Furthermore IL1 beta completely suppressed PB induction of all CYP mRNAs analyzed. Our results demonstrate that IL1 beta can suppress basal CYP activities, as well as PB-inducible expression of five CYP mRNAs in rat hepatocytes in primary culture.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2B1
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / genetics
  • Enzyme Induction / drug effects
  • Humans
  • Interleukin-1 / pharmacology*
  • Interleukin-6 / pharmacology
  • Liver / drug effects*
  • Liver / enzymology
  • Male
  • Oxidoreductases / biosynthesis
  • Oxidoreductases / genetics
  • Phenobarbital / antagonists & inhibitors*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology


  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Recombinant Proteins
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2B1
  • Phenobarbital