In vitro effects of eicosanoids derived from different 20-carbon fatty acids on production of monocyte-derived cytokines in human whole blood cultures

Introduction: Prostaglandins (PG) and leukotrienes (LT) are usually formed from arachidonic acid (e.g. PGE2, LTB4, LTC4). 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. PGE3, LTC5). 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 48 h with lipopolysaccharide. PGE and LT were added and the concentrations of inflammatory cytokines in the cell culture supernatants determined.Results: Tumour necrosis factor (TNF)-? concentrations were significantly decreased by the addition of PGE. At the maximum concentration used (10?6 M) TNF-? concentration was reduced to 100%, 90% and 70% by PGE1, PGE2 and PGE3 respectively. Likewise, interleukin (IL)-1? concentration was decreased to 60%, 30% and 40% by 10?6 M PGE1, PGE2 and PGE3, respectively. IL-6 and IL-10 concentrations were not altered by PG. LTB4, LTC4 or LTC5 did not significantly affect cytokine concentrations.Conclusions: PGE inhibit lipopolysaccharide-stimulated TNF-? and IL-1? production in human whole blood cultures. PGE1, PGE2 and PGE3 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