Dihomo‐γ‐linolenic acid inhibits tumour necrosis factor‐α production by human leucocytes independently of cyclooxygenase activity

Abstract

SUMMARYDietary oils (such as borage oil), which are rich in g-linolenic acid (GLA), have been shown to be bene®cial under in¯ammatory conditions. Dihomo-GLA (DGLA) is synthesized directly from GLA and forms a substrate for cyclooxygenase (COX) enzymes, resulting in the synthesis of lipid mediators (eicosanoids). In the present study, the immunomodulatory effects of DGLA were investigated and compared with those of other relevant fatty acids. Freshly isolated human peripheral blood mononuclear cells (PBMC) were cultured in fatty acid (100 mM)-enriched medium for 48 hr. Subsequently, cells were stimulated with lipopolysaccharide (LPS) for 20 hr and the cytokine levels were measured, in supernatants, by enzyme-linked immunosorbent assay (ELISA). Phospholipids were analysed by gas chromatography. Fatty acids were readily taken up, metabolized and incorporated into cellular phospholipids. Compared with the other fatty acids tested, DGLA exerted pronounced modulatory effects on cytokine production. Tumour necrosis factor-a (TNF-a) and interleukin (IL)-10 levels were reduced to 60% of control levels, whereas IL-6 levels were not affected by DGLA. Kinetic studies showed that peak levels of TNF-a, occurring early after LPS addition, were inhibited strongly, whereas IL-10 levels were not affected until 15 hr after stimulation. Both the reduction of cytokine levels and the decrease in arachidonic acid levels in these cells, induced by DGLA, were dose dependent, suggesting a shift in eicosanoidsubtype synthesis. However, although some DGLA-derived eicosanoids similarly reduced TNF-a levels, the effects of DGLA were probably not mediated by COX products, as the addition of indomethacin did not alter the effects of DGLA. In conclusion, these results suggest that DGLA affects cytokine production by human PBMC independently of COX activation.

Borage oil attenuates progression of cardiac remodeling in rats after myocardial infarction

“…The findings of this study suggest that Borage Treatment with Borage oil prostaglandin increases the ratio E1/E2 by raising the availability of prostaglandin E1 via dihomogamma-linolenic acid metabolism, and its can be modulate beneficially inflammatory response due to prostaglandin with anti-thrombotic and anti-proliferative properties 7,19 . The administration of prostaglandin E1…”

“…Dihomo-gamma-linolenic acid can modulate the inflammatory response via T-lymphocytes and monocytes, while reducing secretion of tumor necrosis factor and interleukin 1 and 2, independently of prostaglandin formation 9,19 . The findings of this study suggest that Borage Treatment with Borage oil prostaglandin increases the ratio E1/E2 by raising the availability of prostaglandin E1 via dihomogamma-linolenic acid metabolism, and its can be modulate beneficially inflammatory response due to prostaglandin with anti-thrombotic and anti-proliferative properties 7,19 .…”

Heterologous Production of Dihomo-γ-Linolenic Acid in Saccharomyces cerevisiae

“…Recently, a C 20 PUFA with three double bonds, dihomo-␥-linolenic acid (DGLA) (20:3n-6), has attracted great interest because it has unique biological activities in addition to its importance as a precursor of a large family of anti-inflammatory eicosanoids, such as series 1 prostaglandins and thromboxanes (6,9,12,17,18,20,34,39,41,45). C 20 fatty acids such as DGLA (20:3n-6) are synthesized by sequential desaturation and elongation of dietary LA (18:2n-6) (3,14,24,33).…”

Perturbations in Blood Phosphatidylcholine and Sphingomyelin Fatty Acid Composition in a Sample Population of Cigarette Smokers

“…We observed a significant reduction of DGLA in pPC, ePC, pSM and eSM. Experimental studies have demonstrated the anti-atherosclerotic [52], anti-inflammatory [53] and antidyskinetic [54] effects of DGLA.…”