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Production of interleukin-1 receptor antagonist and interleukin-1 beta by
peripheral blood mononuclear cells is differentially regulated
DD Poutsiaka, BD Clark, E Vannier and CA Dinarello
Department of Medicine, New England Medical Center Hospitals, Boston, MA.
We studied the relationship between the production of the 23-Kd
interleukin-1 receptor antagonist (IL-1ra) and IL-1 beta in cultures of
human peripheral blood mononuclear cells (PBMC) using a specific
radioimmunoassay for IL-1ra that had a sensitivity of 166 +/- 11 pg/mL.
PBMC cultured without human serum made little IL-1ra or IL-1 beta. In the
presence of 1% AB serum, there was no increase in IL-1 beta (0.25 +/- 0.13
ng/mL) but IL-1ra production increased sevenfold to 3.4 +/- 0.5 ng/mL. IgG
(2.5 to 100 micrograms/mL IgG) or granulocyte-macrophage colony-stimulating
factor (GM-CSF) (1 to 100 ng/mL) had no significant effect on IL-1 beta
production but increased IL-1ra production up to 18- fold (18.2 +/- 3.9
ng/mL). Using endotoxin as a stimulant, 82% +/- 2% of IL-1ra was secreted
in comparison with 52% +/- 9% of IL-1 beta. Culture conditions of PBMC
influenced the production of IL-1ra but not IL-1 beta. Rocking
endotoxin-stimulated PBMC produced 75% less IL-1ra but the same amount of
IL-1 beta when compared with PBMC cultured in stationary plastic tubes.
Rocking IgG-or GM-CSF-stimulated PBMC also produced 75% to 80% less IL-1ra.
GM-CSF or IL-1 beta at concentrations that elicited submaximal production
of IL-1ra potentiated IgG-induced IL-1ra production. The production of
IL-1ra and IL-1 beta are under differential regulation because serum, IgG,
and GM-CSF were potent stimuli for the production of IL-1ra but not IL-1
beta, and the prevention of cell-cell contact of PBMC reduced IL-1ra but
not IL-1 beta production.
Volume 78,
Issue 5,
pp. 1275-1281,
09/01/1991
Copyright © 1991 by The American Society of Hematology
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