Fatty acids, the immune response, and autoimmunity: A question of n−6 essentiality and the balance between n−6 and n−3

Abstract

The essentiality of n-6 polyunsaturated fatty acids (PUFA) is described in relation to a thymus/thymocyte accretion of arachidonic acid (20:4n-6, AA) in early development, and the high requirement of lymphoid and other cells of the immune system for AA and linoleic acid (1 8:2n-6, LA) for membrane phospholipids. Low n-6 PUFA intakes enhance whereas high intakes decrease certain immune functions. Evidence from in vitro and in vivo 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-like immune response. In contrast to the effects of the oxidative metabolites of AA, the longer-chain n-6 PUFA produced by gamma-linolenic acid (18:3n-6, GLA) feeding decreases the Th2 cytokine and immunoglobulin (Ig)G1 antibody response. The n-6 PUFA, GLA, dihomo-gamma-linolenic acid (20:3n-6, DHLA) and AA, and certain oxidative metabolites of AA can also induce T-regulatory cell activity, e.g., transforming growth factor (TGF)-beta-producing T cells; GLA feeding studies also demonstrate reduced proinflammatory interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha production. Low intakes of long-chain n-3 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-chain n-3 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-chain n-3 PUFA from fish oils increase survival and reduce disease severity in spontaneous autoantibody-mediated disease, whereas high-fat LA-rich diets increase disease severity. In experimentally induced T cell-mediated autoimmune disease, EFAD diets or diets supplemented with long-chain n-3 PUFA augment disease, whereas n-6 PUFA prevent or reduce the severity. In contrast, in both T cell- and antibody-mediated autoimmune disease, the desaturated/elongated metabolites of LA are protective. PUFA of both the n-6 and n-3 families are clinically useful in human autoimmune-inflammatory disorders, but the precise mechanisms by which these fatty acids exert their clinical effects are not well understood. Finally, the view that all n-6 PUFA are proinflammatory requires revision, in part, and their essential regulatory and developmental role in the immune system warrants appreciation.

Adult neurogenesis and cell cycle regulation in the crustacean olfactory pathway: from glial precursors to differentiated neurons

“…The ratio of omega-3 to omega-6 fatty acids has been proposed to alter neurogenesis by influencing membrane fluidity (Yehuda et al 1998) and/or the structure of membrane proteins (Bourre et al 1991). The omega-3:omega-6 ratio also modulates cytokine and neurotrophin levels (Harbige 2003), which in turn regulate neuronal proliferation and cell fate (Beck et al 2005). …”

Effect of Dietary Oils on Lymphocyte Immunological Activity in Psychologically Stressed Mice

“…9,20) The decrease in AA content of immunocompetent cells is accompanied by reductions in the lymphocyte proliferative response, inflammatory cytokine production and NK cell activity. 11,21) Thus, in the olive oil-fed mice, the isolation stress-induced reduction in the lymphocyte proliferative response and IFN-secretion from lymphocytes may have been, at least partly, due to the decrease in AA content of the lymphocytes.…”

Essential fats for future health. Proceedings of the 9th Unilever Nutrition Symposium, 26–27 May 2010

“…This has made it difficult to identify with certainty the effects of fatty acids on the immune response, although many effects of fatty acids have been reported upon specific components of the response. It is known that EFA deficiency impairs cellular aspects of the immune response (Harbige, 2003). Incorporation of certain fatty acids into immune cell membranes can affect membrane structure and function including raft formation and signalling processes leading to gene expression, and can alter the profile of lipid mediators being produced (Shaikh and Edidin, 2006;Yaqoob and Calder, 2007;Calder, 2008;Kim et al, 2010).…”