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Low n\u22126 PUFA intakes enhance whereas high intakes decrease certain immune functions. Evidence from <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> studies for a role of AA metabolites in immune cell development and functions shows that they can limit or regulate cellular immune reactions and can induce deviation toward a T helper (Th)2\u2010like immune response. In contrast to the effects of the oxidative metabolites of AA, the longer\u2010chain n\u22126 PUFA produced by \u03b3\u2010linolenic acid (18\u22363n\u22126, GLA) feeding decreases the Th2 cytokine and immunoglobulin (Ig)G1 antibody response. The n\u22126 PUFA, GLA, dihomo\u2010\u03b3\u2010linolenic acid (20\u22363n\u22126, DHLA) and AA, and certain oxidative metabolites of AA can also induce T\u2010regulatory cell activity, e.g., transforming growth factor (IGF)\u2010\u03b2\u2010producing T cells; GLA feeding studies also demonstrate reduced proinflammatory interleukin (IL)\u20101 and tumor necrosis factor (TNF)\u2010\u03b1 production. Low intakes of long\u2010chain n\u22123 fatty acids (fish oils) enhance certain immune functions, whereas high intakes are inhibitory on a wide range of functions, e.g., antigen presentation, adhesion molecule expression, Th1 and th2 responses, proinflammatory cytokine and eicosanoid production, and they induce lymphocyte apoptosis. Vitamin E has a demonstrable critical role in long\u2010chain n\u22123 PUFA interactions with immune functions, often reversing the effects of fish oil. The effect of dietary fatty acids on animal autoimmune disease models depends on both the autoimmune model and the amount and type of fatty acids fed. Diets low in fat, essential fatty acid deficient (EFAD), or high in long\u2010chain n\u22123 PUFA from fish oils increase survival and reduce disease severity in spontaneous autoantibody\u2010mediated disease, whereas high\u2010fat LA\u2010rich diets increase disease severity. In experimentally induced T cell\u2010mediated autoimmune disease, EFAD diets or diets supplemented with long\u2010chain n\u22123 PUFA augment disease, whereas n\u22126 PUFA prevent or reduce the severity. In contrast, in both T cell\u2010 and antibody\u2010mediated autoimmune disease, the desaturated\/elongated metabolites of LA are protective. PUFA of both the n\u22126 and n\u22123 families are clinically useful in human autoimmune\u2010inflammatory disorders, but the precise mechanisms by which these fatty acids exert their clinical effects are not well understood. Finally, the view that all n\u22126 PUFA are proinflammatory requires revision, in part, and their essential regulatory and developmental role in the immune system warrants appreciation.<\/jats:p>","DOI":"10.1007\/s11745-003-1067-z","type":"journal-article","created":{"date-parts":[[2006,12,6]],"date-time":"2006-12-06T11:25:37Z","timestamp":1165404337000},"page":"323-341","source":"Crossref","is-referenced-by-count":263,"title":["Fatty acids, the immune response, and autoimmunity: A question of n\u22126 essentiality and the balance between n\u22126 and n\u22123"],"prefix":"10.1002","volume":"38","author":[{"given":"Laurence S.","family":"Harbige","sequence":"first","affiliation":[{"name":"School of Chemical and Life Sciences University of Greenwich at Medway Chatham Maritime Kent ME4 4TB UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,4]]},"reference":[{"key":"e_1_2_2_2_1","first-page":"210","volume-title":"Immunophysiology","author":"Oppenheim J.J.","year":"1990"},{"key":"e_1_2_2_3_1","first-page":"83","volume-title":"Immunology","author":"Roitt I.","year":"1998"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.07.040189.001045"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(96)80606-2"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(97)01053-0"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(92)90083-J"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.6.2259"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1998-47-1.00383.x"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1079\/PNS19980073"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1079\/PNS19980081"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1079\/PNS2001123"},{"issue":"31","key":"e_1_2_2_13_1","first-page":"100","article-title":"On the Essentiality of Omega\u20103 Polyunsaturated Fatty Acids","volume":"38","author":"Rivers J.","year":"1984","journal-title":"Br. 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