Antiinflammatory properties of hepatic acute phase proteins: Preferential induction of interleukin 1 (IL-1) receptor antagonist over IL-1β synthesis by human peripheral blood mononuclear cells

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Abstract

This study was undertaken to determine whether acute phase proteins (APP) induce the synthesis of interleukin 1β (IL-1β) and its specific antagonist, IL-1 receptor antagonist (IL-1Ra), in human peripheral blood mononuclear cells (PBMC). PBMC from healthy volunteers were incubated with C-reactive protein (CRP), α1-antitrypsin (α1-AT), or α1-acid glycoprotein (AGP), and the levels of IL-1β and IL-1Ra produced were measured by specific radioimmunoassay. To evaluate the effects of α1-AT further, a synthetic pentapeptide FVYLI corresponding to the minimal binding sequence for the serpine-enzyme complex receptor was also evaluated. PBMC incubated for 24 h with CRP, α1-AT, or the pentapeptide FVYLI synthesized large quantities of IL-1Ra, 5-10-fold greater than the amount of IL-1β produced by these cells. AGP induced significantly less IL-1Ra than the other APP tested. These effects were shown to be specific, in that polyclonal antibodies against CRP, α1-AT, and AGP eliminated the cytokine production induced by these respective proteins. CRP, α1-AT, FVYLI, and AGP were synergistic with low concentrations of endotoxin in the induction of both IL-1Ra and IL-1β synthesis. We suggest that the preferential induction of IL-1Ra by APP may contribute to their antiinflammatory effects and provide an important regulatory signal for the acute phase response.

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Tilg, H., Vannier, E., Vachino, G., Dinarello, C. A., & Mier, J. W. (1993). Antiinflammatory properties of hepatic acute phase proteins: Preferential induction of interleukin 1 (IL-1) receptor antagonist over IL-1β synthesis by human peripheral blood mononuclear cells. Journal of Experimental Medicine, 178(5), 1629–1636. https://doi.org/10.1084/jem.178.5.1629

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