Leukotrienes do not regulate interleukin 1 production by activated macrophages.
The objective of this work was to investigate the role of leukotrienes in the production of IL-1 by activated human peripheral blood monocytes and mouse peritoneal macrophages. Using overnight adherent macrophages, stimulation with lipopolysaccharide or zymosan caused a time-dependent increase in IL-1 production. LTC4 was detected and preceded IL-1 production only in zymosan-treated macrophages. Lipopolysaccharide did not stimulate macrophages to produce LTC4. Zymosan-stimulated LTC4 production was inhibited by the lipoxygenase inhibitors, ICI207968 (3.20 microM), nordihydroguaiaretic acid (0.22 microM), phenidone (4.60 microM), REV5901 (0.20 microM), and the Merck 5-lipoxygenase "translocation inhibitor" MK886 (0.02 microM) with IC50 values as shown in parenthesis. However, none of these inhibitors reduced IL-1 production at concentrations which completely inhibited leukotriene synthesis. Taken together, these results do not support a role for leukotrienes in the production of IL-1 by zymosan-activated macrophages.
Parkar
B A
BA
ICI Pharmaceuticals, Bioscience I, Macclesfield, Chesire, UK.
McCormick
M E
ME
Foster
S J
SJ
D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors; D002448:Cell Adhesion; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000276:immunology*; D013189:SRS-A / Q000096:biosynthesis / Q000502:physiology*; D015054:Zymosan / Q000494:pharmacology*
D001095:Arachidonic Acids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D013189:SRS-A; D015054:Zymosan; D015232:Dinoprostone