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

J Nutr Biochem. 2007 Apr;18(4):250-8. doi: 10.1016/j.jnutbio.2006.04.003. Epub 2006 Jun 16.


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 kappaB (NF-kappaB) activation in human THP-1 monocyte-derived macrophages. Pretreatment with 100 microM EPA and DHA significantly decreased lipopolysaccharide (LPS)-stimulated THP-1 macrophage tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta and IL-6 production (P<.02), compared to control cells. Both EPA and DHA reduced TNF-alpha, IL-1beta 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 microM) of DHA had a greater inhibitory effect than that of EPA on macrophage IL-1beta (P<.01 and P<.04, respectively) and IL-6 (P<.003 and P<.003, respectively) production following 0.01 and 0.1 microg/ml LPS stimulation. Both EPA and DHA down-regulated LPS-induced NF-kappaB/DNA binding in THP-1 macrophages by approximately 13% (P< or =.03). DHA significantly decreased macrophage nuclear p65 expression (P< or =.05) and increased cytoplasmic IkappaBalpha expression (P< or =.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-kappaB. Further work is required to elucidate additional divergent mechanisms to account for apparent differences between EPA and DHA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line
  • Docosahexaenoic Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Eicosapentaenoic Acid / pharmacology*
  • Humans
  • I-kappa B Proteins / biosynthesis
  • Inflammation / prevention & control*
  • Interleukin-1beta / biosynthesis
  • Interleukin-6 / biosynthesis
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / physiology*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Anti-Inflammatory Agents, Non-Steroidal
  • I-kappa B Proteins
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • NFKBIA protein, human
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid