Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6

Hepatology. 1990 Nov;12(5):1179-86. doi: 10.1002/hep.1840120517.


Human hepatocytes in primary culture were used as a model system to investigate the mechanism(s) involved in the induction of the acute-phase response in human liver. Hepatocytes were incubated with increasing amounts of recombinant human interleukin-1 beta, recombinant interleukin-6 and tumor necrosis factor-alpha. Synthesis of C-reactive protein was studied at the mRNA and protein levels. Only recombinant interleukin-6 was capable of inducing C-reactive protein-mRNA and C-reactive protein-protein synthesis. Also, fibrinogen and alpha-1-antitrypsin synthesis measured by immunoprecipitation with specific antisera increased in a dose-dependent, time-dependent manner, whereas albumin synthesis decreased to about 50% of controls. Maximal effects were observed at 100 to 300 units of recombinant interleukin-6/ml culture medium after 20 hr of incubation. Although the synthetic glucocorticoid dexamethasone slightly modulated the effect of recombinant interleukin-6, it was not an absolute requirement for the induction of acute-phase protein synthesis in human hepatocytes. In pulse-chase experiments it was shown that the time course of the disappearance of the acute-phase proteins from the cells and their appearance in the medium is not influenced by recombinant interleukin-6. This finding suggests that recombinant interleukin-6 exerts its regulatory effect on acute-phase protein synthesis at the pretranslational level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / biosynthesis*
  • Acute-Phase Reaction / metabolism*
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism
  • Dexamethasone / pharmacology
  • Fibrinogen / metabolism
  • Humans
  • Interleukin-1 / pharmacology
  • Interleukin-6 / pharmacology*
  • Liver / metabolism*
  • Liver / pathology
  • RNA, Messenger / metabolism
  • Serum Albumin / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • alpha 1-Antitrypsin / metabolism


  • Acute-Phase Proteins
  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Serum Albumin
  • Tumor Necrosis Factor-alpha
  • alpha 1-Antitrypsin
  • Dexamethasone
  • Fibrinogen
  • C-Reactive Protein