Regulation of synthesis and secretion of major rat acute-phase proteins by recombinant human interleukin-6 (BSF-2/IL-6) in hepatocyte primary cultures.

The regulation of the three major acute-phase proteins α2-macroglobulin, cysteine proteinase inhibitor and α1-antitrypsin by recombinant human interleukin-1β, recombinant human interleukin-6 and recombinant human tumor necrosis factor α was studied in rat hepatocyte primary cultures. Synthesis and secretion of the acute-phase proteins was measured after labeling with [35S]methionine and immunoprecipitation. Incubation of hepatocytes with interleukin-6 led to dose-dependent and time-dependent changes in the synthesis of the three major acute-phase proteus and albumin, similar to those occurring m vivo during experimental inflammation. α2-Macroglobulin and cysteine proteinase inhibitor synthesis was induced 54-fold and 8-fold, respectively, 24 h after the addition of 100 units/ml interleukin-6. At the same time synthesis of the negative acute-phase protein albumin was reduced to 30% of controls. Half-maximal effects were achieved with 4 units interleukin-6/ml. Interleukin-lβ bad only a partial effect on the regulation of the fore proteins studied: only a twofold stimulation of α2-macroglobulin and a 60% reduction of albumin synthesis were observed. Tumor necrosis factor α did not alter the synthesis of acute-phase proteins. The stimulation of α2-macroglobulin and cysteine proteinase inhibitor synthesis by interleukin-6 was inhibited by interleukin-lβ in a dose-dependent manner. In pulse-chase experiments the effect of interleukin-lβ, interleukin-6 and tumor necrosis factor a on the secretion of acute-phase proteins was examined. Interleukin-6 markedly accelerated the secretion of total proteins and α2-macroglobulin, whereas the secretion of cysteine proteinase inhibitor, α1-antitrypsin and albumin was not affected. The inhibition of N-glycosylation by tunicamycin abolished the effect of interleukin-6 on the secretion of α2-macroglobulin, indicating a possible role of interleukin-6 on N-glycosylation. [ABSTRACT FROM AUTHOR]