Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men

Kelley, Darshan S.; Taylor, Peter; Nelson, Gary J.; Mackey, Bruce E.

doi:10.1007/s11745-998-0187-9

Cited by 132 publications

(99 citation statements)

References 32 publications

(37 reference statements)

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“…However, production of TNFa, IL-1b and IL-6 by the latter was not found to be significantly altered (Kelley et al 1998a). Similarly, ARA was found to have no effect on mitogen-stimulated T-cell proliferation (Kelley et al 1997), NK cell activity (Kelley et al 1997) or IL-2 production by mitogen-stimulated T-cells (Kelley et al 1998a). Thus, increased ARA intake may result in changes indicative of selectively increased inflammation or inflammatory responses in man.…”

Section: Dietary Fatty Acids the Inflammatory Response And T-cell-mementioning

confidence: 95%

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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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Section: Dietary Fatty Acids the Inflammatory Response And T-cell-mementioning

confidence: 95%

“…The influence of increased dietary ARA has been investigated in two studies in healthy human subjects. In one study (Kelley et al 1998a) healthy young males supplemented their diets with 1 . 5 g ARA/d for 7 weeks.…”

Section: Dietary Fatty Acids the Inflammatory Response And T-cell-mementioning

confidence: 99%

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

Sijben¹,

2007

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“…In vitro AA supplementation stimulates PG release and skeletal muscle cell hypertrophy via a COX-2-dependent pathway. arachidonic acid; C2C12; growth; nonsteroidal anti-inflammatory drug; skeletal muscle ARACHIDONIC ACID (AA) is a polyunsaturated -6 fatty acid [20:4(6)], present in the diet, that is incorporated into cell membrane phospholipids (PLs) (19). Dietary change elicits rapid alterations in PL fatty acid composition, with supplemental AA increasing plasma PL abundance within days (42).…”

mentioning

confidence: 99%

Arachidonic acid supplementation enhances in vitro skeletal muscle cell growth via a COX-2-dependent pathway

Markworth

Cameron‐Smith

2013

American Journal of Physiology-Cell Physiology

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[e.g., prostaglandins (PGs), leukotrienes, and hydroxyeicosatetraenoic acids] has been implicated in skeletal muscle cell growth and development. The collective role of AA-derived metabolites in physiological states of skeletal muscle growth/atrophy remains unclear. The present study aimed to determine the direct effect of free AA supplementation and subsequent eicosanoid biosynthesis on skeletal myocyte growth in vitro. C2C12 (mouse) skeletal myocytes induced to differentiate with supplemental AA exhibited dose-dependent increases in the size, myonuclear content, and protein accretion of developing myotubes, independent of changes in cell density or the rate/extent of myogenic differentiation. Nonselective (indomethacin) or cyclooxygenase 2 (COX-2)-selective (NS-398) nonsteroidal anti-inflammatory drugs blunted basal myogenesis, an effect that was amplified in the presence of supplemental free AA substrate. The stimulatory effects of AA persisted in preexisting myotubes via a COX-2-dependent (NS-389-sensitive) pathway, specifically implying dependency on downstream PG biosynthesis. AAstimulated growth was associated with markedly increased secretion of PGF 2␣ and PGE2; however, incubation of myocytes with PG-rich conditioned medium failed to mimic the effects of direct AA supplementation. In vitro AA supplementation stimulates PG release and skeletal muscle cell hypertrophy via a COX-2-dependent pathway. arachidonic acid; C2C12; growth; nonsteroidal anti-inflammatory drug; skeletal muscle ARACHIDONIC ACID (AA) is a polyunsaturated -6 fatty acid [20:4(6)], present in the diet, that is incorporated into cell membrane phospholipids (PLs) (19). Dietary change elicits rapid alterations in PL fatty acid composition, with supplemental AA increasing plasma PL abundance within days (42). In response to cellular perturbation (e.g., mechanical trauma, cytokines, or growth factors), AA is cleaved from PL molecules via the action of the enzyme PLA 2 . Free intracellular AA serves as a key transient cell-signaling intermediate, undergoing rapid enzymatic conversion to a diverse array of inflammatory autocrine/paracrine eicosanoid lipid mediators. Parallel cyclooxygenase (COX-1/COX-2) and lipoxygenase (5-LOX/ 12-LOX/15-LOX) pathways catalyze the oxidation of AA to ultimately produce the PGs (PGD 2 , PGE 2 , PGF 2␣ , PGI 2 , and thromboxane A 2 ) and the leukotriene (LT)/lipoxin (LX) families of eicosanoids, respectively. Nonsteroidal anti-inflammatory drugs (NSAIDs) are thought to exert their anti-inflammatory, analgesic, and antipyretic action, specifically by inhibition of the COX branch of the AA pathway, indicative of a central role of PG species in mediating the inflammatory response.Skeletal muscle cells express the COX genes COX-1 and COX-2 (49) and locally synthesize/release AA-derived PGs, including PGD 2 (56), PGE 2 /PGF 2␣ (33,40,41,54), and PGI 2 (2). NSAID treatment is associated with deleterious effects on adaptive skeletal muscle growth/regeneration (3, 4, 31, 39 -41, 46), consistent with the inflammatory res...

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“…In other words, lymphoproliferation would be enhanced, and thereby inflammation will become more severe due to increased LTB4-mediated immune cell chemotaxis to foci of inflammation. While eicosanoid production is elevated by arachidonic acid supplementation to human subjects, it did not influence cytokine secretion or the antibody response to influenza vacccine (Kelley et al 1998). Furthermore, feeding arachidonic acid to healthy mice had similar effects to safflower oil feeding, while EPA and DHA fed in parallel suppressed T lymphocyte function, signal transduction and gene expression (Jolly et al 1997.…”

Section: Intracellular Signalling Pathways Influenced By N-3 Fatty Acidsmentioning

confidence: 96%

The effects of dietary lipids on gene expression and apoptosis

1998

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Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men

Cited by 132 publications

References 32 publications

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

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

Arachidonic acid supplementation enhances in vitro skeletal muscle cell growth via a COX-2-dependent pathway

The effects of dietary lipids on gene expression and apoptosis

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