title: Dietary long-chain omega-3 fatty acids do not diminish eosinophilic pulmonary inflammation in mice.
abstract: Although the effects of fish oil supplements on airway inflammation in asthma have been studied with varying results, the independent effects of the fish oil components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), administered separately, are untested. Here, we investigated airway inflammation and hyperresponsiveness using a mouse ovalbumin exposure model of asthma assessing the effects of consuming EPA (1.5% wt/wt), DHA (1.5% wt/wt), EPA plus DHA (0.75% each), or a control diet with no added omega-3 polyunsaturated fatty acids. Consuming these diets for 6 weeks resulted in erythrocyte membrane EPA contents (molar %) of 9.0 (± 0.6), 3.2 (± 0.2), 6.8 (± 0.5), and 0.01 (± 0.0)%; DHA contents were 6.8 (± 0.1), 15.6 (± 0.5), 12.3 (± 0.3), and 3.8 (± 0.2)%, respectively. The DHA group had the highest bronchoalveolar lavage (BAL) fluid eosinophil and IL-6 levels (P < 0.05). Similar trends were seen for macrophages, IL-4, and IL-13, whereas TNF-α was lower in omega-3 polyunsaturated fatty acid groups than the control (P < 0.05). The DHA group also had the highest airway resistance, which differed significantly from the EPA plus DHA group (P < 0.05), which had the lowest. Oxylipins were measured in plasma and BAL fluid, with DHA and EPA suppressing arachidonic acid-derived oxylipin production. DHA-derived oxylipins from the cytochrome P450 and 15-lipoxygenase pathways correlated significantly with BAL eosinophil levels. The proinflammatory effects of DHA suggest that the adverse effects of individual fatty acid formulations should be thoroughly considered before any use as therapeutic agents in asthma.
authors.affiliation: 1 United States Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Immunity and Disease Prevention Unit, Davis, California.
authors.forename: Gertrud U
authors.initials: GU
authors.lastname: Schuster
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bratt
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Jiang
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Pedersen
authors.forename: Dmitry
authors.initials: D
authors.lastname: Grapov
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Adkins
authors.forename: Darshan S
authors.initials: DS
authors.lastname: Kelley
authors.forename: John W
authors.initials: JW
authors.lastname: Newman
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Kenyon
authors.forename: Charles B
authors.initials: CB
authors.lastname: Stephensen
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000633:toxicity; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000633:toxicity; D001249:Asthma / Q000097:blood / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements / Q000633:toxicity; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology* / Q000633:toxicity; D015118:Eicosapentaenoic Acid / Q000494:pharmacology* / Q000633:toxicity; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D054883:Oxylipins / Q000378:metabolism; D011014:Pneumonia / Q000097:blood / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D011657:Pulmonary Eosinophilia / Q000097:blood / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D054883:Oxylipins; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid