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

This study was undertaken to determine whether acute phase proteins (A PP) induce the synthesis of interleukin 1beta (IL-1beta) and its speci fic antagonist, IL-1 receptor antagonist (IL-1Ra), in human peripheral blood mononuclear cells (PBMC). PBMC from healthy volunteers were inc ubated with C-reactive protein (CPP), alpha1-antitrypsin (alpha1-AT), or alpha1-acid glycoprotein (AGP), and the levels of IL-1beta and IL-1 Ra produced were measured by specific radioimmunoassay. To evaluate th e effects of alpha1-AT further, a synthetic pentapeptide FVYLI corresp onding to the minimal binding sequence for the serpine-enzyme complex receptor was also evaluated. PBMC incubated for 24 h with CRP, alpha1- AT, or the pentapeptide FVYLI synthesized large quantities of IL-1Ra, 5-10-fold greater than the amount of IL-1beta produced by these cells. AGP induced significantly less IL-1Ra than the other APP tested. Thes e effects were shown to be specific, in that polyclonal antibodies aga inst CRP, alpha1-AT, and AGP eliminated the cytokine production induce d by these respective proteins. CRP, alpha1-AT, FVYLI, and AGP were sy nergistic with low concentrations of endotoxin in the induction of bot h IL-1Ra and IL-1beta synthesis. We suggest that the preferential indu ction of IL-1Ra by APP may contribute to their antiinflammatory effect s and provide an important regulatory signal for the acute phase respo nse.