Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on immune cell composition and function in healthy humans

Kew, Samantha; Mesa, Maria Dolores; Tricon, Sabine; Buckley, Richard; Minihane, Anne Marie; Yaqoob, Parveen

doi:10.1093/ajcn/79.4.674

Cited by 211 publications

(163 citation statements)

References 23 publications

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“…In vivo studies investigating effects of n-3 PUFAs on peripheral blood mononuclear cells showed no reduction of TNF-␣ and other cytokine production by oral PUFA uptake (35), but a significant decrease when using a n-3 PUFA-enriched lipid infusion (36). However, IL-12 is exclusively produced by professional APCs and is essential for differentiation of Th1 cells and promotes activation of NK cells (37).…”

Section: Discussionmentioning

confidence: 99%

Polyunsaturated Fatty Acids Block Dendritic Cell Activation and Function Independently of NF-κB Activation

Zeyda

Säemann

Stuhlmeier³

et al. 2005

Journal of Biological Chemistry

128

110

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Polyunsaturated fatty acids (PUFAs) modulate immune responses leading to clinically significant beneficial effects in a variety of inflammatory disorders. PUFA effects on T cells have been extensively studied, but their influence on human dendritic cells (DCs), which are the most potent antigen-presenting cells and play a key role in initiating immune responses, has not been elucidated so far. Here we show that PUFAs of the n-3 and n-6 series (arachidonic and eicosapentaenoic acid) affect human monocyte-derived DC differentiation and inhibit their activation by LPS, resulting in altered DC surface molecule expression and diminished cytokine secretion. Furthermore, the potency to stimulate T cells was markedly inhibited in PUFA-treated DCs. The PUFA-mediated block in LPS-induced DC activation is reflected by diminished TNF-␣, IL-12p40, CD40, and COX-2 mRNA levels. Strikingly, typical LPS-induced signaling events such as degradation of IB and activation of NF-B were not affected by PUFAs, even though DC membrane lipid composition was markedly altered. Arachidonic and eicosapentaenoic acid both altered DC prostaglandin production, but inhibitors of cyclooxygenases and lipoxygenases did not abolish PUFA effects, indicating that the observed PUFA actions on DCs were independent of autoregulation via eicosanoids. These data demonstrate a unique interference with DC activation and function that could significantly contribute to the well known anti-inflammatory effects of PUFAs.

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Section: Discussionmentioning

confidence: 99%

Polyunsaturated Fatty Acids Block Dendritic Cell Activation and Function Independently of NF-κB Activation

Zeyda

Säemann

Stuhlmeier³

et al. 2005

Journal of Biological Chemistry

128

110

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“…For instance, changes in outcomes reported may occur over time. The observation by Kew et al (2004) is noteworthy in that it shows that in the absence of effects on cytokines CD69 expression, a marker of T-cell activation, is reduced by 4 . 9 g DHA/d but not by 4 .…”

Section: Effects Of Epa and Dha On Natural Killer Cell Activitymentioning

confidence: 95%

Differential immunomodulation with long-chainn-3 PUFA in health and chronic disease

Sijben¹,

2007

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The balance of intake of n-6 and n-3 PUFA, and consequently their relative incorporation into immune cells, is important in determining the development and severity of immune and inflammatory responses. Some disorders characterised by exaggerated inflammation and excessive formation of inflammatory markers have become among the most important causes of death and disability in man in modern societies. The recognition that long-chain n-3 PUFA have the potential to inhibit (excessive) inflammatory responses has led to a large number of clinical investigations with these fatty acids in inflammatory conditions as well as in healthy subjects. The present review explores the presence of dose-related effects of long-chain n-3 PUFA supplementation on immune markers and differences between healthy subjects and those with inflammatory conditions, because of the important implications for the transfer of information gained from studies with healthy subjects to patient populations, e.g. for establishing dose levels for specific applications. The effects of long-chain n-3 PUFA supplementation on ex vivo lymphocyte proliferation and cytokine production by lymphocytes and monocytes in healthy subjects have been studied in twenty-seven, twenty-five and forty-six treatment cohorts respectively, at intake levels ranging from 0 . 2 g EPA + DHA/d to 7 . 0 g EPA + DHA/d. Most studies, particularly those with the highest quality study design, have found no effects on these immune markers. Significant effects on lymphocyte proliferation are decreased responses in seven of eight cohorts, particularly in older subjects. The direction of the significant changes in cytokine production by lymphocytes is inconsistent and only found at supplementation levels ‡ 2 . 0 g EPA + DHA/d. Significant changes in inflammatory cytokine production by monocytes are decreases in their production in all instances. Overall, these studies fail to reveal strong dose-response effects of EPA + DHA on the outcomes measured and suggest that healthy subjects are relatively insensitive to immunomodulation with longchain n-3 PUFA, even at intake levels that substantially raise their concentrations in phospholipids of immune cells. In patients with inflammatory conditions cytokine concentrations or production are influenced by EPA + DHA supplementation in a relatively large number of studies. Some of these studies suggest that local effects at the site of inflammation might be more pronounced than systemic effects and disease-related markers are more sensitive to the immunomodulatory effects, indicating that the presence of inflamed tissue or 'sensitised' immune cells in inflammatory disorders might increase sensitivity to the immunomodulatory effects of long-chain n-3 PUFA. In a substantial number of these studies clinical benefits related to the inflammatory state of the condition have been observed in the absence of significant effects on immune markers of inflammation. This finding suggests that conditionspecific clinical end points might be more sensitive markers...

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“…As such, individuals from populations traditionally with this type of diet have a high percentage of the omega-6 fatty acid arachidonic acid and very low fractions of the omega-3 fatty acid eicosapentaenoic acid (EPA) within their inflammatory cells (Gibney and Hunter 1993;Sperling et al 1993). However, dietary supplementation with omega-3 fatty acids increases the fraction of omega-3s EPA and docosahezaenoic acid (DHA) within the plasma membrane of cells (De Caterina et al 1994;Kew et al 2004;Meydani et al 1993;Mickleborough et al 2006;Mickleborough et al 2003;Sperling et al 1993) which subsequently produces less biologically active inflammatory mediators (Calder 2003;Obata et al 1999). …”

Section: Introductionmentioning

confidence: 99%

The effects of short-term fish oil supplementation on pulmonary function and airway inflammation following a high-fat meal

2013

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Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on immune cell composition and function in healthy humans

Abstract: Supplementation with DHA, but not with EPA, suppresses T lymphocyte activation, as assessed by expression of CD69. EPA alone does not, therefore, influence CD69 expression. No other marker of immune function assessed in this study was significantly affected by either EPA or DHA.

Cited by 211 publications

References 23 publications

Polyunsaturated Fatty Acids Block Dendritic Cell Activation and Function Independently of NF-κB Activation

Polyunsaturated Fatty Acids Block Dendritic Cell Activation and Function Independently of NF-κB Activation

Differential immunomodulation with long-chainn-3 PUFA in health and chronic disease

The effects of short-term fish oil supplementation on pulmonary function and airway inflammation following a high-fat meal

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