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  • Title: Regulation of hepatic acute phase protein synthesis by products of interleukin 2 (IL 2)-stimulated human peripheral blood mononuclear cells.
    Author: Mier JW, Dinarello CA, Atkins MB, Punsal PI, Perlmutter DH.
    Journal: J Immunol; 1987 Aug 15; 139(4):1268-72. PubMed ID: 2440951.
    Abstract:
    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.
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