Lipids

, Volume 38, Issue 4, pp 323–341 | Cite as

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

Articles

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 (18∶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 γ-linolenic acid (18∶3n−6, GLA) feeding decreases the Th2 cytokine and immunoglobulin (Ig)G1 antibody response. The n−6 PUFA, GLA, dihomo-γ-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 (IGF)-β-producing T cells; GLA feeding studies also demonstrate reduced proinflammatory interleukin (IL)-1 and tumor necrosis factor (TNF)-α 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.

Abbreviations

AA

arachidonic acid

ALA

α-linolenic acid

APC

antigen-presenting cells

CREAE

chronic relapsing EAE

DHA

docosahexaenoic acid

DHLA

dihomo-γ-linolenic acid

DTH

delayed-type hypersensitivity

EAE

experimental autoimmune encephalomyelitis

EAU

experimental autoimmune uveitis

EFAD

essential fatty acid deficiency

EPA

eicosapentaenoic acid

GLA

γ-linolenic acid

IL

interleukin

INF

interferon

LA

linoleic acid

LFA

leucocyte function-associated antigen

LT

leukotriene

MHC

major histocompatibility complex

NK

natural killer

PG

prostaglandin

PHA

phytohemagglutinin

RA

rheumatoid arthritis

ROI

reactive oxygen intermediates

SLE

systemic lupus erythematosus

TcR

T cell antigen receptor

TGF

transforming growth factor

Th

T helper

TNF

tumor necrosis factor

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© AOCS Press 2003

Authors and Affiliations

  1. 1.School of Chemical and Life SciencesUniversity of Greenwich at MedwayChatham MaritimeUK

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