In vitro effects of eicosanoids derived from different 20-carbon Fatty acids on production of monocyte-derived cytokines in human whole blood cultures.
BACKGROUND
Prostaglandins (PG) and leukotrienes (LT) are usually formed from arachidonic acid (e.g. PGE(2), LTB(4), LTC(4)). The anti-inflammatory effects of fish oil may be mediated through the production of alternative PG and/or LT formed from eicosapentaenoic acid (e.g. PGE(3), LTC(5)). This study examines the effects of PG and LT derived from different fatty acid precursors on lipopolysaccharide-induced cytokine production by cultured human whole blood. Methods Human whole blood was diluted 1:5 and incubated for 48h with lipopolysaccharide. PGE and LT were added and the concentrations of inflammatory cytokines in the cell culture supernatants determined.


RESULTS
Tumour necrosis factor (TNF)-alpha concentrations were significantly decreased by the addition of PGE. At the maximum concentration used (10(-6)M) TNF-alpha concentration was reduced to 100%, 90% and 70% by PGE(1), PGE(2) and PGE(3) respectively. Likewise, interleukin (IL)-1beta concentration was decreased to 60%, 30% and 40% by 10(-6)M PGE(1), PGE(2) and PGE(3), respectively. IL-6 and IL-10 concentrations were not altered by PG. LTB(4), LTC(4) or LTC(5) did not significantly affect cytokine concentrations.


CONCLUSIONS
PGE inhibit lipopolysaccharide-stimulated TNF-alpha and IL-1beta production in human whole blood cultures. PGE(1), PGE(2) and PGE(3) show a similar pattern and magnitude of effect. This suggests that the anti-inflammatory effects of dietary fish oil may not be mediated through a simple substitution of one family of eicosanoids for another.
Miles
E A
EA
Institute of Human Nutrition, University of Southampton, Southampton, UK. eam@soton.ac.uk
Allen
E
E
Calder
P C
PC
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D004537:Eicosanoic Acids / Q000378:metabolism*; D015777:Eicosanoids / Q000378:metabolism*; D004731:Endotoxins / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004537:Eicosanoic Acids; D015777:Eicosanoids; D004731:Endotoxins; D008070:Lipopolysaccharides; D011458:Prostaglandins E; D014409:Tumor Necrosis Factor-alpha; D007213:Indomethacin