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

• Published in: The Journal of nutritional biochemistry Vol. 18; no. 4; pp. 250 - 258
• Main Authors: Weldon, Sinéad M., Mullen, Anne C., Loscher, Christine E., Hurley, Lisa A., Roche, Helen M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2007; Elsevier Science
• Subjects: anti-inflammatory activity; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Cell Line; Cytokines; Docosahexaenoic acid; Docosahexaenoic Acids - pharmacology; Dose-Response Relationship, Drug; Eicosapentaenoic acid; Eicosapentaenoic Acid - pharmacology; Feeding. Feeding behavior; fish oils; Fundamental and applied biological sciences. Psychology; Humans; I-kappa B Proteins - biosynthesis; immunostimulants; Inflammation - prevention & control; interleukin-1; Interleukin-1beta - biosynthesis; interleukin-6; Interleukin-6 - biosynthesis; Lipopolysaccharides - pharmacology; Macrophage; macrophage activation; macrophages; Macrophages - drug effects; Macrophages - physiology; messenger RNA; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; Nuclear factor κB; nutrition-genotype interaction; omega-3 fatty acids; RNA, Messenger - metabolism; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - biosynthesis; Vertebrates: anatomy and physiology, studies on body, several organs or systems; DON; Cytokines; DMSO; DTT; PMA; Docosahexaenoic acid; NF-κB; PMSF; EMSA; FBS; EPA; DHA; GAPDH; Eicosapentaenoic acid; LC PUFA; Macrophage; Nuclear factor κB; Human; Nuclear factor KB; Vertebrata; Mammalia; Antiinflammatory agent; Cytokine; Lipopolysaccharide
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2006.04.003

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.