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 (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.
Tilg
H
H
Department of Medicine, New England Medical Center, Boston, Massachusetts.
Vannier
E
E
Vachino
G
G
Dinarello
C A
CA
Mier
J W
JW
D000209:Acute-Phase Proteins / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D009961:Orosomucoid / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D000209:Acute-Phase Proteins; D000894:Anti-Inflammatory Agents, Non-Steroidal; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007376:Interleukin-2; D008070:Lipopolysaccharides; D009842:Oligopeptides; D009961:Orosomucoid; D012795:Sialoglycoproteins; D000515:alpha 1-Antitrypsin; D002097:C-Reactive Protein