{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T18:17:53Z","timestamp":1778955473074,"version":"3.51.4"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 (\u00b1 0.6), 3.2 (\u00b1 0.2), 6.8 (\u00b1 0.5), and 0.01 (\u00b1 0.0)%; DHA contents were 6.8 (\u00b1 0.1), 15.6 (\u00b1 0.5), 12.3 (\u00b1 0.3), and 3.8 (\u00b1 0.2)%, respectively. The DHA group had the highest bronchoalveolar lavage (BAL) fluid eosinophil and IL-6 levels (P &amp;lt; 0.05). Similar trends were seen for macrophages, IL-4, and IL-13, whereas TNF-\u03b1 was lower in omega-3 polyunsaturated fatty acid groups than the control (P &amp;lt; 0.05). The DHA group also had the highest airway resistance, which differed significantly from the EPA plus DHA group (P &amp;lt; 0.05), which had the lowest. Oxylipins were measured in plasma and BAL fluid, with DHA and EPA suppressing arachidonic acid\u2013derived 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.<\/jats:p>","DOI":"10.1165\/rcmb.2013-0136oc","type":"journal-article","created":{"date-parts":[[2013,10,17]],"date-time":"2013-10-17T15:58:39Z","timestamp":1382025519000},"page":"626-636","source":"Crossref","is-referenced-by-count":35,"title":["Dietary Long-Chain Omega-3 Fatty Acids Do Not Diminish Eosinophilic Pulmonary Inflammation in Mice"],"prefix":"10.1093","volume":"50","author":[{"given":"Gertrud U.","family":"Schuster","sequence":"first","affiliation":[{"name":"United States Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Immunity and Disease Prevention Unit, Davis, California"},{"name":"Nutrition Department, University of California, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Bratt","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of California, Davis, California; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Jiang","sequence":"additional","affiliation":[{"name":"United States Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Immunity and Disease Prevention Unit, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa L.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"USDA, ARS, Western Human Nutrition Research Center, Obesity and Metabolism Research Prevention, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry","family":"Grapov","sequence":"additional","affiliation":[{"name":"Nutrition Department, University of California, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuriko","family":"Adkins","sequence":"additional","affiliation":[{"name":"United States Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Immunity and Disease Prevention Unit, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darshan S.","family":"Kelley","sequence":"additional","affiliation":[{"name":"United States Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Immunity and Disease Prevention Unit, Davis, California"},{"name":"Nutrition Department, University of California, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W.","family":"Newman","sequence":"additional","affiliation":[{"name":"Nutrition Department, University of California, Davis, California"},{"name":"USDA, ARS, Western Human Nutrition Research Center, Obesity and Metabolism Research Prevention, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Kenyon","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of California, Davis, California; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles B.","family":"Stephensen","sequence":"additional","affiliation":[{"name":"United States Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Immunity and Disease Prevention Unit, Davis, California"},{"name":"Nutrition Department, University of California, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,3,1]]},"reference":[{"key":"2026030623192853600_bib1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1159\/000228999","article-title":"Effects of fat and fatty acid intake on inflammatory and immune responses: a critical review","volume":"55","author":"Galli","year":"2009","journal-title":"Ann Nutr Metab"},{"key":"2026030623192853600_bib2","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1111\/j.1398-9995.2009.02042.x","article-title":"Omega 3 and 6 oils for primary prevention of allergic disease: systematic review and meta-analysis","volume":"64","author":"Anandan","year":"2009","journal-title":"Allergy"},{"key":"2026030623192853600_bib3","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1111\/j.1471-0528.2010.02846.x","article-title":"The effect of perinatal omega-3 fatty acid supplementation on inflammatory markers and allergic diseases: a systematic review","volume":"118","author":"Klemens","year":"2011","journal-title":"BJOG"},{"key":"2026030623192853600_bib4","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/(SICI)1097-4547(19981215)54:6<805::AID-JNR8>3.0.CO;2-4","article-title":"Docosahexaenoic acid decreases phospholipase A2 activity in the neurites\/nerve growth cones of PC12 cells","volume":"54","author":"Martin","year":"1998","journal-title":"J Neurosci Res"},{"key":"2026030623192853600_bib5","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/j.1399-3038.2004.00187.x","article-title":"Effect of omega-3 fatty acid concentrations in plasma on symptoms of asthma at 18 months of age","volume":"15","author":"Mihrshahi","year":"2004","journal-title":"Pediatr Allergy Immunol"},{"key":"2026030623192853600_bib6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1097\/MCP.0b013e3283323b73","article-title":"Diet and asthma","volume":"16","author":"Raviv","year":"2010","journal-title":"Curr Opin Pulm Med"},{"key":"2026030623192853600_bib7","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1472-6882-6-26","article-title":"Treating asthma with omega-3 fatty acids: where is the evidence? A systematic review","volume":"6","author":"Reisman","year":"2006","journal-title":"BMC Complement Altern Med"},{"key":"2026030623192853600_bib8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0899-9007(99)00256-7","article-title":"Effect of individual fatty acids of omega-6 and omega-3 type on human immune status and role of eicosanoids","volume":"16","author":"Kelley","year":"2000","journal-title":"Nutrition"},{"key":"2026030623192853600_bib9","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1159\/000074898","article-title":"Immunomodulation by polyunsaturated fatty acids: mechanisms and effects","volume":"132","author":"Stulnig","year":"2003","journal-title":"Int Arch Allergy Immunol"},{"key":"2026030623192853600_bib10","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.plipres.2007.12.004","article-title":"The opposing effects of n-3 and n-6 fatty acids","volume":"47","author":"Schmitz","year":"2008","journal-title":"Prog Lipid Res"},{"key":"2026030623192853600_bib11","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.bbrc.2010.08.025","article-title":"Protective effect of resolvin E1 on the development of asthmatic airway inflammation","volume":"400","author":"Aoki","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"2026030623192853600_bib12","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.atc.2006.01.003","article-title":"Novel chemical mediators in the resolution of inflammation: resolvins and protectins","volume":"24","author":"Serhan","year":"2006","journal-title":"Anesthesiol Clin"},{"key":"2026030623192853600_bib13","first-page":"115","article-title":"Novel eicosanoid and docosanoid mediators: resolvins, docosatrienes, and neuroprotectins","volume":"8","author":"Serhan","year":"2005","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"2026030623192853600_bib14","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/ni.1627","article-title":"Resolvin E1 regulates interleukin 23, interferon-gamma and lipoxin A4 to promote the resolution of allergic airway inflammation","volume":"9","author":"Haworth","year":"2008","journal-title":"Nat Immunol"},{"key":"2026030623192853600_bib15","first-page":"227","article-title":"Cell\u2013cell interaction in the transcellular biosynthesis of novel omega-3\u2013derived lipid mediators","volume":"341","author":"Chiang","year":"2006","journal-title":"Methods Mol Biol"},{"key":"2026030623192853600_bib16","doi-asserted-by":"crossref","first-page":"8491","DOI":"10.1073\/pnas.0402531101","article-title":"Neuroprotectin D1: a docosahexaenoic acid\u2013derived docosatriene protects human retinal pigment epithelial cells from oxidative stress","volume":"101","author":"Mukherjee","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026030623192853600_bib17","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.1172\/JCI25420","article-title":"A role for docosahexaenoic acid\u2013derived neuroprotectin D1 in neural cell survival and Alzheimer disease","volume":"115","author":"Lukiw","year":"2005","journal-title":"J Clin Invest"},{"key":"2026030623192853600_bib18","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jasms.2006.09.002","article-title":"Resolvin D1, protectin D1, and related docosahexaenoic acid\u2013derived products: analysis via electrospray\/low energy tandem mass spectrometry based on spectra and fragmentation mechanisms","volume":"18","author":"Hong","year":"2007","journal-title":"J Am Soc Mass Spectrom"},{"key":"2026030623192853600_bib19","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1084\/jem.20020760","article-title":"Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals","volume":"196","author":"Serhan","year":"2002","journal-title":"J Exp Med"},{"key":"2026030623192853600_bib20","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0090-6980(02)00047-3","article-title":"Lipoxins and aspirin-triggered 15-epi-lipoxin biosynthesis: an update and role in anti-inflammation and pro-resolution","volume":"68-69","author":"Serhan","year":"2002","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"2026030623192853600_bib21","doi-asserted-by":"crossref","first-page":"496","DOI":"10.4049\/jimmunol.178.1.496","article-title":"Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness","volume":"178","author":"Levy","year":"2007","journal-title":"J Immunol"},{"key":"2026030623192853600_bib22","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1096\/fj.06-6250fje","article-title":"Docosahexaenoic acid (DHA) blunts liver injury by conversion to protective lipid mediators: protectin D1 and 17S-hydroxy-DHA","volume":"20","author":"Gonz\u00e1lez-P\u00e9riz","year":"2006","journal-title":"FASEB J"},{"key":"2026030623192853600_bib23","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.clnu.2008.10.012","article-title":"Eicosapentaenoic acid is more effective than docosahexaenoic acid in inhibiting proinflammatory mediator production and transcription from LPS-induced human asthmatic alveolar macrophage cells","volume":"28","author":"Mickleborough","year":"2009","journal-title":"Clin Nutr"},{"key":"2026030623192853600_bib24","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.4049\/jimmunol.180.3.1834","article-title":"Vitamin A deficiency decreases and high dietary vitamin A increases disease severity in the mouse model of asthma","volume":"180","author":"Schuster","year":"2008","journal-title":"J Immunol"},{"key":"2026030623192853600_bib25","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1093\/bioinformatics\/bts439","article-title":"imDEV: a graphical user interface to r multivariate analysis tools in microsoft excel","volume":"28","author":"Grapov","year":"2012","journal-title":"Bioinformatics"},{"key":"2026030623192853600_bib26","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1089\/met.2011.0113","article-title":"Docosahexaenoic acid prevents trans-10, cis-12\u2013conjugated linoleic acid\u2013induced nonalcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation","volume":"10","author":"Fedor","year":"2012","journal-title":"Metab Syndr Relat Disord"},{"key":"2026030623192853600_bib27","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/j.1753-4887.2004.tb00021.x","article-title":"Fish oil and inflammatory disease: is asthma the next target for n-3 fatty acid supplements?","volume":"62","author":"Stephensen","year":"2004","journal-title":"Nutr Rev"},{"issue":"2, Suppl 2","key":"2026030623192853600_bib28","doi-asserted-by":"crossref","first-page":"S95","DOI":"10.1016\/j.jaci.2009.10.047","article-title":"Asthma: clinical expression and molecular mechanisms","volume":"125","author":"Lemanske","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"2026030623192853600_bib29","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.freeradbiomed.2009.05.033","article-title":"Dietary supplementation of omega-3 fatty acid\u2013containing fish oil suppresses F2-isoprostanes but enhances inflammatory cytokine response in a mouse model of ovalbumin-induced allergic lung inflammation","volume":"47","author":"Yin","year":"2009","journal-title":"Free Radic Biol Med"},{"issue":"6 Suppl","key":"2026030623192853600_bib30","doi-asserted-by":"crossref","first-page":"1505S","DOI":"10.1093\/ajcn\/83.6.1505S","article-title":"n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases","volume":"83","author":"Calder","year":"2006","journal-title":"Am J Clin Nutr"},{"key":"2026030623192853600_bib31","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1159\/000053645","article-title":"Effect of aerosolized docosahexaenoic acid in a mouse model of atopic asthma","volume":"123","author":"Yokoyama","year":"2000","journal-title":"Int Arch Allergy Immunol"},{"key":"2026030623192853600_bib32","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1165\/rcmb.2010-0156OC","article-title":"Docosahexaenoic acid derivative prevents inflammation and hyperreactivity in lung: implication of PKC-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kD in asthma","volume":"45","author":"Morin","year":"2011","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026030623192853600_bib33","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1111\/cea.12162","article-title":"Mag-epa resolves lung inflammation in an allergic model of asthma","volume":"43","author":"Morin","year":"2013","journal-title":"Clin Exp Allergy"},{"key":"2026030623192853600_bib34","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.bbadis.2011.05.002","article-title":"Fat-1 transgenic mice with elevated omega-3 fatty acids are protected from allergic airway responses","volume":"1812","author":"Bilal","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"2026030623192853600_bib35","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1093\/jn\/132.12.3566","article-title":"(n-3) Fatty acids and infectious disease resistance","volume":"132","author":"Anderson","year":"2002","journal-title":"J Nutr"},{"key":"2026030623192853600_bib36","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1086\/650344","article-title":"Transgenic mice enriched in omega-3 fatty acids are more susceptible to pulmonary tuberculosis: impaired resistance to tuberculosis in fat-1 mice","volume":"201","author":"Bonilla","year":"2010","journal-title":"J Infect Dis"},{"key":"2026030623192853600_bib37","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.nut.2005.06.006","article-title":"Dietary fatty acids modulate chronic colitis, colitis-associated colon neoplasia and COX-2 expression in IL-10 knockout mice","volume":"22","author":"Hegazi","year":"2006","journal-title":"Nutrition"},{"key":"2026030623192853600_bib38","doi-asserted-by":"crossref","first-page":"7960","DOI":"10.1158\/0008-5472.CAN-10-1396","article-title":"Dietary fish oil alters T lymphocyte cell populations and exacerbates disease in a mouse model of inflammatory colitis","volume":"70","author":"Woodworth","year":"2010","journal-title":"Cancer Res"},{"key":"2026030623192853600_bib39","first-page":"357","article-title":"The role of eosinophils in allergic airway inflammation","volume":"9","author":"Walsh","year":"2010","journal-title":"Discov Med"},{"key":"2026030623192853600_bib40","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1093\/jn\/135.7.1745","article-title":"Dietary (n-3) polyunsaturated fatty acids modulate murine Th1\/Th2 balance toward the Th2 pole by suppression of Th1 development","volume":"135","author":"Zhang","year":"2005","journal-title":"J Nutr"},{"key":"2026030623192853600_bib41","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1126\/science.290.5499.2140","article-title":"Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain","volume":"290","author":"de Urquiza","year":"2000","journal-title":"Science"},{"key":"2026030623192853600_bib42","doi-asserted-by":"crossref","first-page":"7916","DOI":"10.4049\/jimmunol.175.12.7916","article-title":"Retinoid x receptor agonists increase bcl2a1 expression and decrease apoptosis of naive T lymphocytes","volume":"175","author":"Rasooly","year":"2005","journal-title":"J Immunol"},{"key":"2026030623192853600_bib43","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/ejcn.2011.39","article-title":"Associations of obesity with triglycerides and C-reactive protein are attenuated in adults with high red blood cell eicosapentaenoic and docosahexaenoic acids","volume":"65","author":"Makhoul","year":"2011","journal-title":"Eur J Clin Nutr"},{"key":"2026030623192853600_bib44","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.coph.2007.03.001","article-title":"TNF-alpha in asthma","volume":"7","author":"Berry","year":"2007","journal-title":"Curr Opin Pharmacol"},{"key":"2026030623192853600_bib45","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.jaci.2007.10.028","article-title":"Targeting TNF-alpha: a novel therapeutic approach for asthma","volume":"121","author":"Brightling","year":"2008","journal-title":"J Allergy Clin Immunol"},{"key":"2026030623192853600_bib46","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.pupt.2009.10.007","article-title":"TNF-alpha inhibitors in asthma and COPD: we must not throw the baby out with the bath water","volume":"23","author":"Matera","year":"2010","journal-title":"Pulm Pharmacol Ther"},{"key":"2026030623192853600_bib47","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.plefa.2009.05.004","article-title":"Toxicology and safety of DHA","volume":"81","author":"Lien","year":"2009","journal-title":"Prostaglandins Leukot Essent Fatty Acids"},{"key":"2026030623192853600_bib48","doi-asserted-by":"crossref","first-page":"804S","DOI":"10.3945\/jn.108.101329","article-title":"Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids","volume":"139","author":"Harris","year":"2009","journal-title":"J Nutr"},{"key":"2026030623192853600_bib49","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/nm.2678","article-title":"Asthma phenotypes: the evolution from clinical to molecular approaches","volume":"18","author":"Wenzel","year":"2012","journal-title":"Nat Med"}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/50\/3\/626\/67114796\/ajrcmb_50_3_626.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/50\/3\/626\/67114796\/ajrcmb_50_3_626.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T04:19:51Z","timestamp":1772857191000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/50\/3\/626\/8492606"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,1]]},"references-count":49,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2014,3,1]]},"published-print":{"date-parts":[[2014,3,1]]}},"URL":"https:\/\/doi.org\/10.1165\/rcmb.2013-0136oc","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,3]]},"published":{"date-parts":[[2014,3,1]]}}}