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Abstract
The present study attempted to determine the effect of dietary supplementation with evening primrose seed oil (EPO) enriched with γ-linolenic acid (GLA, 18:3n-6) on the synthesis of proinflammatory 5-lipoxygenase (5-LOX) metabolites of arachidonic acid (AA, 20:4n-6) by human peripheral neutrophils in adults with atopic dermatitis (AD). After incubation of neutrophils with calcium ionophore A-23187 (10 μM) the 5-LOX products were separated and quantified by reversed-phase high-performance liquid chromatography (RP-HPLC). The results demonstrated that neutrophils of AD patients without therapy generated significantly less LTB4 (P < 0.05) and 5-HETE (P < 0.01) than cells from healthy controls. A significant increase in proinflammatory LTB4 (P > 0.01) and 5-HETE (P < 0.05) was revealed in AD patients after 12 weeks of daily ingestion of 6 g EPO, equivalent to 0.48 g GLA per day, compared with untreated patients (LTB4 609 ± 173 pmol/107 cells vs 390 ± 84 pmol/107 cells and 5-HETE 1463 ± 418 pmol/107 cells vs 946 ± 129 pmol/107 cells). In contrast the level of AA in the phospholipids of neutrophils was unaltered, whereas the level of dihomo-γ-linolenic acid (DGLA, 20:3n-6), an elongation product of GLA, was significantly elevated (P < 0.01). The synthesis of 15-hydroxyeicosatrienoic acid (15-HETrE), an anti-inflammatory metabolite of DGLA, was not observed. The AA/DGLA ratio in the phospholipids of neutrophils decreased within 12 weeks of EPO treatment and was negatively correlated with the molar sum of 5-LOX metabolites in the indicated time interval (r = -0.88, n = 6). It is therefore reasonable to speculate that the availability of AA in membrane phospholipids of neutrophils is impaired in AD patients. Our results indicate that treatment with EPO probably improves the release of AA and consequently increases the generation of 5-LOX products to normal levels in neutrophils of patients with AD. The pathophysiological significance of these results remains to be clarified.