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
H. Tilg et al., 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, The Journal of experimental medicine, 178(5), 1993, pp. 1629-1636
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.