Human whole blood interleukin-1-beta production: kinetics, cell source, and comparison with TNF-alpha.
Because removal of monocytes from their natural milieu may alter their subsequent immune response patterns, we have compared the production of interleukin-1 beta (IL-1-beta) and tumor necrosis factor alpha (TNF-alpha) by cultured human whole blood to that by purified monocytes. IL-1-beta was released in a dose-dependent fashion by whole blood after stimulation with lipopolysaccharide. Immunofluorescence studies indicated that monocytes were the main producers of IL-1-beta in whole blood cultures. On a per monocyte basis, after stimulation with 10 micrograms/ml lipopolysaccharide, much more IL-1-beta was released by cultured whole blood (56.2 +/- 8.3 ng/10(6) monocytes) than by purified mononuclear cells maintained in tissue culture medium (7.1 +/- 2.6 ng/10(6) monocytes). However, maintaining purified mononuclear cells in autologous plasma restored IL-1-beta release to levels observed in whole blood cultures. IL-1-beta release by whole blood peaked at 9 to 12 hours, in contrast to release of TNF-alpha, which peaked at 6 hours. In parallel with protein production, IL-1-beta messenger RNA levels peaked later and were more sustained than TNF-alpha messenger RNA levels. These experiments suggest that plasma augments the stimulatory effect of endotoxin and that IL-1-beta and TNF-alpha have differing kinetics in whole blood.
Allen
J N
JN
Department of Internal Medicine, Ohio State University, Columbus.
Herzyk
D J
DJ
Allen
E D
ED
Wewers
M D
MD
D001773:Blood Cells / Q000378:metabolism*; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000097:blood*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D009000:Monocytes / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha