Immunomodulation by omega-3 fatty acids

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Abstract

The immune system, including its inflammatory components, is fundamental to host defense against pathogenic invaders. It is a complex system involving interactions amongst many different cell types dispersed throughout the body. Central to its actions are phagocytosis, processing of antigens derived from intracellular and extracellular pathogens, activation of T cells with proliferation and production of cytokines that elicit effector cell functions such as antibody production and killing cell activity. Inappropriate immunologic activity, including inflammation, is a characteristic of many common human disorders. Eicosanoids produced from arachidonic acid have roles in inflammation and regulation of T and B lymphocyte functions. Eicosapentaenoic acid (EPA) also gives rise to eicosanoids and docosahexaenoic acid (DHA) to docosanoids; these may have differing properties to arachidonic acid-derived eicosanoids. EPA and DHA give rise to newly discovered resolvins. Human immune cells are typically rich in arachidonic acid, but arachidonic acid, EPA and DHA contents can be altered through oral administration of those fatty acids. This results in a change pattern of production of eicosanoids and probably also of docosanoids and resolvins, although the latter are not well examined in the human context. Changing the fatty acid composition of immune cells also affects phagocytosis, T-cell signaling and antigen presentation capability. These effects appear to mediated at the membrane level suggesting important roles of fatty acids in membrane order, lipid raft structure and function and membrane trafficking.

Introduction

The purpose of this article is to collate and review observations from studies investigating the effects of polyunsaturated fatty acids (PUFAs), especially n-3 PUFAs, on selected aspects of the immune response, highlighting some recent findings. This is not a comprehensive review of all aspects of immunity that have been studied in the context of altered PUFA exposure. Such comprehensive reviews can be found elsewhere [1], [2], [3], [4], [5].

Section snippets

The immune system—an overview

The immune system protects the host from environmental infectious agents such as pathogenic bacteria, viruses, fungi, and parasites and from other noxious insults. It also permits tolerance to self-antigens and to non-threatening environmental agents such as food proteins and commensal gut bacteria. The system has two functional divisions: the innate (or natural) immune system and the acquired (also termed specific or adaptive) immune system. Both components involve various blood-borne factors

The fatty acid composition of immune cells

The phospholipids of immune cells (such as lymph node or splenic lymphocytes or peritoneal macrophages) taken from rodents maintained on normal laboratory chow typically contain 15–20% of fatty acids as arachidonic acid and contain very little very long chain n-3 fatty acids [10], [11]. Modifying the fatty acid composition of the diet of such animals leads to altered fatty acid composition of the immune cells, typically with increased appearance of the fatty acid(s) in which the diet has become

Roles of fatty acids in immune cells

Fatty acids fulfill a variety of roles within immune cells. They act as:

  • fuels for generation of energy;

  • components of cell membrane phospholipids contributing to the physical and functional properties of those membranes;

  • covalent modifiers of protein structure influencing the cellular location and function of proteins;

  • regulators of gene expression either through effects on receptor activity, on intracellular signaling processes, or on transcription factor activation;

  • precursors for synthesis of

Modification of lipid mediator profiles

Because of the relatively high amount of arachidonic acid in immune cell membrane phospholipids, this fatty acid is typically the major precursor for eicosanoid mediators, which are produced in greatly increased amounts upon cellular stimulation. Thus, amongst the mix of eicosanoids produced, those synthesized from arachidonic acid (e.g. PGE2 and LTB4) predominate although the exact eicosanoid profile depends upon the cell type concerned (e.g. neutrophils and mast cells produce a lot of PGD2

Conclusions

The immune system, including its inflammatory components, is fundamental to host defense against pathogenic invaders. It is a complex system involving interactions amongst many different cell types dispersed throughout the body. Central to its actions are phagocytosis of bacteria, processing of antigens derived from intracellular and extracellular pathogens, activation of T cells with clonal expansion (proliferation) and production of cytokines that elicit effector cell functions such as

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