Docosahexaenoic Acid and Eicosapentaenoic Acid Supplementation Differentially Modulate Pro- and Anti-inflammatory Cytokines in Subjects with Chronic Inflammation (OR29-02-19)

Abstract

ObjectivesDespite extensive works on the cardioprotective effects of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the distinct mechanisms by which DHA and EPA modulate inflammation and plasma lipids are not well characterized. We compared the effects of DHA and EPA supplementation on serum cytokines and blood monocyte inflammatory response and on blood lipids in subjects with chronic inflammation. MethodsTwenty-one subjects (9 men and 12 women, 50–75 y) with chronic inflammation (CRP > 2 μg/mL) were enrolled in a randomized, controlled crossover trial consisting of a 4-week lead-in control phase (high oleic sunflower oil, 3 g/d) followed by two sequential 10-week supplementation phases with pure DHA or EPA (3 g/d each) with a 10-week washout in between. Serum concentrations of cytokines were determined by electrochemiluminescence (ECL) assay. Following lipopolysaccharides (LPS) stimulation of blood monocytes, gene expression and secretion of cytokines were assessed by qPCR and ECL. Plasma lipid concentrations were measured by enzymatic assays. ResultsRelative to the control phase, DHA reduced the LPS-induced gene expression of pro-inflammatory TNFA (median % change: –45%, P < 0.001), IL6 (–51%, P < 0.05), MCP1 (–28%, P < 0.04) as well as anti-inflammatory IL10 (–33%, P < 0.02) and the secretion of TNF-α (–41%, P < 0.02), MCP-1 (–29%, P < 0.01), and IL-10 (–47%, P < 0.05) in monocytes. On the other hand, EPA increased serum concentrations of IL-10 (+14%, P < 0.05) and lowered only TNFAexpression (–20%, P < 0.03) in monocytes. When compared to EPA supplementation, DHA decreased serum concentrations of MCP-1 (P < 0.03), and monocyte MCP-1 secretion (P < 0.05) and IL10 expression (P < 0.04). Regarding plasma concentrations of lipids, relative to the control phase, both DHA (–16%, P < 0.001) and EPA decreased triglycerides (–22%, P < 0.001) while only DHA increased LDL-cholesterol (+7%, P < 0.02). ConclusionsDHA and EPA differently modulate the balance between pro- and anti-inflammatory cytokines in serum and blood monocytes in subjects with chronic inflammation. While DHA inhibits a broad range of pro- and anti-inflammatory cytokines, EPA has a relatively minor role in lowering pro-inflammatory cytokines but preserves the anti-inflammatory IL-10. DHA, but not EPA, increases LDL-cholesterol. Funding SourcesFunded by USDA/NIFA.