Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids

Abstract

1. Fish oils are rich in the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. Linseed oil and green plant tissues are rich in the precursor fatty acid, alpha-linolenic acid (18:3n-3). Most vegetable oils are rich in the n-6 PUFA linoleic acid (18:2n-6), the precursor of arachidonic acid (20:4n-6). 2. Arachidonic acid-derived eicosanoids such as prostaglandin E2 are pro-inflammatory and regulate the functions of cells of the immune system. Consumption of fish oils leads to replacement of arachidonic acid in cell membranes by eicosapentaenoic acid. This changes the amount and alters the balance of eicosanoids produced. 3. Consumption of fish oils diminishes lymphocyte proliferation, T-cell-mediated cytotoxicity, natural killer cell activity, macrophage-mediated cytotoxicity, monocyte and neutrophil chemotaxis, major histocompatibility class II expression and antigen presentation, production of pro-inflammatory cytokines (interleukins 1 and 6, tumour necrosis factor) and adhesion molecule expression. 4. Feeding laboratory animals fish oil reduces acute and chronic inflammatory responses, improves survival to endotoxin and in models of autoimmunity and prolongs the survival of grafted organs. 5. Feeding fish oil reduces cell-mediated immune responses. 6. Fish oil supplementation may be clinically useful in acute and chronic inflammatory conditions and following transplantation. 7. n-3 PUFAs may exert their effects by modulating signal transduction and/or gene expression within inflammatory and immune cells.

Effect of fatty acids on leukocyte function

“…These changes can affect the activity of transmembrane proteins, such as cell receptors and ionic channels (3,4).…”

“…Thus, dihomogamma-linoleic acid and arachidonic acid inhibit the production of IL-2 by lymphocytes, an effect that cannot be abolished by cyclooxygenase inhibitors. Most PUFAs can decrease IL-2 production, particularly of the omega-3 class, and EPA has the highest potency among them, an effect associated with their inhibitory action on lymphocyte proliferation and with lowered expression of IL-2 receptor, with a decrease in naive T cells and a rise in memory T cells (3,24).…”

“…Thus, animals fed diets rich in omega-3 fatty acids (fish oil) and omega-6 fatty acids (olive oil) have decreased expression of LFA-1, ICAM-1 and CD2 (3,31). Pretreatment of lymphocytes with DHA or EPA (omega-3) can reduce the expression of the adhesion molecules Lselectin and LFA-1 (45).…”

“…-PUFAs inhibit antibody synthesis and IL-2 production (3,24,41,43). -Omega-3-rich diets decrease NK and LAK cell activity (14,23,24).…”

“…-Omega-3-rich diets decrease NK and LAK cell activity (14,23,24). -Omega-3 fatty acids decrease adhesion molecule expression and lymphocyte adhesion to the endothelium (3,31,45).…”