Role of interleukin-1beta in the modulations of cytochrome P450 and heme metabolism in rat liver

J Interferon Cytokine Res. 1999 Jun;19(6):601-7. doi: 10.1089/107999099313730.


The effect of recombinant human interleukin-1beta (IL-1beta) on the modulation of hepatic cytochrome P450 (P450) was investigated by in vivo subcutaneous dosing studies in male Sprague-Dawley rats. To assess the effect of IL-1beta on heme metabolism, we determined the delta-aminolevulinic acid synthetase (delta-ALAS) and heme oxygenase activities in the liver. IL-1beta suppressed the microsomal total P450 and heme contents and delta-ALAS activity in the liver. In contrast, microsomal heme oxygenase activity was significantly increased by the IL-1beta treatments. Western blot analysis and marker enzyme activities for individual P450 isoforms demonstrated that IL-1beta suppressed CYP2C6, 2C13, 2E1, and 3A2, whereas CYP2A, 2B1/2, 2C11, and 4A1 were not influenced by the treatments. IL-1beta inhibited both allylisopropylamide- and phenobarbital-inducible delta-ALAS activities in the liver. These results indicate that IL-1beta has differential effects on the constitutive P450, and also on delta-ALAS and heme oxygenase activities in rat liver. Thus, the modulation of hepatic P450 by IL-1beta is complex, and IL-1beta may be involved in the regulation of both apoprotein synthesis for each P450 isoform and the heme pools in the liver.

MeSH terms

  • 5-Aminolevulinate Synthetase / metabolism
  • Animals
  • Blotting, Western
  • Cytochrome P-450 Enzyme System / metabolism*
  • Heme / metabolism*
  • Heme Oxygenase (Decyclizing) / metabolism
  • Humans
  • Interleukin-1 / physiology*
  • Liver / metabolism*
  • Male
  • Phenobarbital / pharmacology
  • Rats
  • Rats, Sprague-Dawley


  • Interleukin-1
  • Heme
  • Cytochrome P-450 Enzyme System
  • Heme Oxygenase (Decyclizing)
  • 5-Aminolevulinate Synthetase
  • Phenobarbital