Regulation of hepatic acute phase protein synthesis by products of interleukin 2 (IL 2)-stimulated human peripheral blood mononuclear cells.
Cancer patients injected with recombinant human IL 2 develop marked changes in serum concentrations of hepatic acute-phase proteins. To determine if this acute-phase response involves a change in the rate of hepatic protein synthesis and if it is due to a direct effect of IL 2 on hepatocytes, human hepatoma-derived hepatocytes (Hep-3B cells) were incubated in medium containing IL 2 or in culture supernatants from IL 2-activated human peripheral blood mononuclear cells (PBMNC). The rate of synthesis of two acute-phase proteins, complement protein factor B and albumin, was determined by the incorporation of a radiolabeled amino acid precursor into newly synthesized protein as measured by analytical gel electrophoresis of immunoprecipitates. IL 2 in concentrations from 1 to 1000 U/ml had no effect on the synthesis of factor B or albumin; conversely, there was a dose-dependent increase in the rate of synthesis of factor B and decrease in albumin synthesis mediated by culture supernatants of IL 2-activated PBMNC. The magnitude of the effect of acute-phase protein synthesis was dependent on the IL 2 concentration used for the activation of PBMNC. The rate of factor B synthesis increased approximately 4.0-fold in the presence of culture supernatants of PBMNC activated with either opsonized heat-killed Staphylococcus albus or with 1000 U/ml IL 2. Preincubation of the IL 2-activated PBMNC culture supernatants with an antiserum specific for recombinant IL 1-beta completely neutralized the capacity of the supernatants to stimulate factor B synthesis, whereas antisera specific for human IL 1-alpha or for tumor necrosis factor had no effect. These results indicate that the indirect effect of IL 2 on hepatic acute phase protein synthesis is mediated by IL 1-beta.
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000818:Animals; D002460:Cell Line; D011415:Complement Factor B / Q000096:biosynthesis; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D008099:Liver / Q000502:physiology*; D008114:Liver Neoplasms, Experimental; D012709:Serum Albumin / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha
D000209:Acute-Phase Proteins; D006023:Glycoproteins; D007375:Interleukin-1; D007376:Interleukin-2; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D011415:Complement Factor B