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  • Title: Antiinflammatory properties of hepatic acute phase proteins: preferential induction of interleukin 1 (IL-1) receptor antagonist over IL-1 beta synthesis by human peripheral blood mononuclear cells.
    Author: Tilg H, Vannier E, Vachino G, Dinarello CA, Mier JW.
    Journal: J Exp Med; 1993 Nov 01; 178(5):1629-36. PubMed ID: 7693853.
    Abstract:
    This study was undertaken to determine whether acute phase proteins (APP) induce the synthesis of interleukin 1 beta (IL-1 beta) 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), alpha 1-antitrypsin (alpha 1-AT), or alpha 1-acid glycoprotein (AGP), and the levels of IL-1 beta and IL-1Ra produced were measured by specific radioimmunoassay. To evaluate the effects of alpha 1-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, alpha 1-AT, or the pentapeptide FVYLI synthesized large quantities of IL-1Ra, 5-10-fold greater than the amount of IL-1 beta 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, alpha 1-AT, and AGP eliminated the cytokine production induced by these respective proteins. CRP, alpha 1-AT, FVYLI, and AGP were synergistic with low concentrations of endotoxin in the induction of both IL-1Ra and IL-1 beta 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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