Dietary supplementation of ω-3 fatty acid-containing fish oil suppresses F2-isoprostanes but enhances inflammatory cytokine response in a mouse model of ovalbumin-induced allergic lung inflammation

Epidemiological and clinical evidence has suggested that increased dietary intake of fish oil containing ω-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be associated with a reduced risk of asthma. However, interventional studies on these effects have been equivocal and controversial. Free radical oxidation products of lipids and cyclooxygenases-derived prostaglandins are believed to play an important role in asthma, and fish oil supplementation may modulate the levels of these critical lipid mediators. We employed a murine model of allergic inflammation produced by sensitization to ovalbumin (OVA) to study the effects of fish oil supplementation on airway inflammation. Our studies demonstrated that ω-3 fatty acids were dose dependently incorporated into mouse lung tissue after dietary supplementation. We examined the oxidative stress status by measuring the levels of isoprostanes (IsoPs), the gold standard for oxidative stress in vivo. OVA challenge caused significant increase of F2-IsoPs in mouse lung, suggesting an elevated level of oxidative stress. Compared to the control group, fish oil supplementation led to a significant reduction of F2-IsoP (from arachidonic acid) with a concomitant increase of F3-IsoPs (from EPA) and F4-IsoPs (from DHA). Surprisingly, however, fish oil supplementation enhanced production of proinflammatory cytokine IL-5 and IL-13. Furthermore, fish oil supplementation suppressed the production of pulmonary protective PGE2 in the bronchoalveolar lavage (BAL) while the level of urinary metabolites of the PGE2 was increased. Our data suggest that augmented lung inflammation after fish oil supplementation may be due to the reduction of PGE2 production in the lung and these dichotomous results bring into question the role of fish oil supplementation in the treatment of asthma.