Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaenoic acid

A number of studies have investigated the effects of fish oil on the production of pro-inflammatory cytokines using peripheral blood mononuclear cell models. The majority of these studies have employed heterogeneous blends of long-chain n−3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which preclude examination of the individual effects of LC n−3 PUFA. This study investigated the differential effects of pure EPA and DHA on cytokine expression and nuclear factor κB (NF-κB) activation in human THP-1 monocyte-derived macrophages. Pretreatment with 100 μM EPA and DHA significantly decreased lipopolysaccharide (LPS)-stimulated THP-1 macrophage tumor necrosis factor (TNF) α, interleukin (IL) 1β and IL-6 production (P<.02), compared to control cells. Both EPA and DHA reduced TNF-α, IL-1β and IL-6 mRNA expression. In all cases, the effect of DHA was significantly more potent than that of EPA (P<.01). Furthermore, a low dose (25 μM) of DHA had a greater inhibitory effect than that of EPA on macrophage IL-1β (P<.01 and P<.04, respectively) and IL-6 (P<.003 and P<.003, respectively) production following 0.01 and 0.1 μg/ml LPS stimulation. Both EPA and DHA down-regulated LPS-induced NF-κB/DNA binding in THP-1 macrophages by ~13% (P≤.03). DHA significantly decreased macrophage nuclear p65 expression (P≤.05) and increased cytoplasmic IκBα expression (P≤.05). Although similar trends were observed with EPA, they were not significant. Our findings suggest that DHA may be more effective than EPA in alleviating LPS-induced pro-inflammatory cytokine production in macrophages — an effect that may be partly mediated by NF-κB. Further work is required to elucidate additional divergent mechanisms to account for apparent differences between EPA and DHA.