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

Abstract

Introduction: 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.