EPA and DHA differentially modulate monocyte inflammatory response in subjects with chronic inflammation in part via plasma specialized pro-resolving lipid mediators: A randomized, double-blind, crossover study

Abstract

Background and aims: The independent effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on chronic inflammation through their downstream lipid mediators, including the specialized pro-resolving lipid mediators (SPM), remain unstudied. Therefore, we compared the effects of EPA and DHA supplementation on monocyte inflammatory response and plasma polyunsaturated fatty acids (PUFA) SPM lipidome.

Methods: After a 4-week lead-in phase (baseline), 9 men and 12 postmenopausal women (50-75 years) with chronic inflammation received two phases of 10-week supplementation with 3 g/day EPA and DHA in a random order, separated by a 10-week washout.

Results: Compared with baseline, EPA and DHA supplementation differently modulated LPS-stimulated monocyte cytokine expression. EPA lowered TNFA (p < 0.001) whereas DHA reduced TNFA (p < 0.001), IL6 (p < 0.02), MCP1 (p < 0.03), and IL10 (p < 0.01). DHA lowered IL10 expression relative to EPA (p = 0.03). Relative to baseline, EPA, but not DHA, decreased the ratios of TNFA/IL10 and MCP1/IL10 (both p < 0.01). EPA and DHA also significantly changed plasma PUFA SPM lipidome by replacing n-6 AA derivatives with their respective derivatives including 18-hydroxy-EPA (+5 fold by EPA) and 17- and 14-hydroxy-DHA (+3 folds by DHA). However, DHA showed a wider effect than EPA by also significantly increasing EPA derivatives and DPA-derived SPM at a greater expense of AA derivatives. Different groups of PUFA derivatives mediated the differential effects of EPA and DHA on monocyte cytokine expression.

Conclusions: EPA and DHA had distinct effects on monocyte inflammatory response with a broader effect of DHA in attenuating pro-inflammatory cytokines. These differential effects were potentially mediated by different groups of PUFA derivatives, suggesting immunomodulatory activities of SPM and their intermediates.

Keywords: DHA; EPA; Inflammation; Monocytes; Randomized crossover trial; Specialized pro-resolving lipid mediators.