ACUTE-PHASE RESPONSE OF HUMAN HEPATOCYTES - REGULATION OF ACUTE-PHASE PROTEIN-SYNTHESIS BY INTERLEUKIN-6

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 interleukin1β;, recombinant interleukin‐6 and tumor necrosis factor‐α. 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 α−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. (HEPATOLOGY 1990;12:1179–1186). Copyright © 1990 American Association for the Study of Liver Diseases