Fatty acids and the immune system : dose response studies with n-3 polyunsaturated fatty acids

Abstract

The studies in this thesis have involved administration of different doses of EPA and DHA to mice (for 7 days) rats (for 6 weeks), and humans (for 6 months). In the animal studies EPA or DHA was fed at 2.2 or 4.4 g/100g total fatty acids, while in the human study EPA+DHA was supplied at 0.7 g or 1.5 g/day. The human study also included two doses of α-LNA (5.0 g and 10.0 g/day). Several aspects of both innate and acquired immunity were investigated. These include the measurement of lipopolysaccharide- and mitogen-elicited cytokines (TNF-α, IL-6, IL-1β, IL-2, IFN-γ, IL-4, and IL-10), monocyte and neutrophil phagocytic and oxidative burst activity, lymphocyte proliferation and the delayed type hypersensitivity response. In addition, the fatty acid compositions of plasma in both animals and humans, as well as blood mononuclear cells in humans and spleen cells in animals were determined.

There were significant dose-dependent increases in the content of n-3 PUFA in rat plasma and rat and mouse spleen cells, when feeding EPA or DHA at 2.2 g/ and 4.4 g/day. There was a significant effect of the position of EPA within dietary triacylglcerol (TAG) on its incorporation into the phospholipid (PL) fraction in murine spleen cells, with a significant increase in EPA content when fed in the sn-2 position. In rats this was only detected when the PL molecular species were analysed. In terms of rat lymphocyte functions there was no effect of EPA or DHA feeding on the production of cytokines, while lymphocyte proliferation was dose-dependently decreased when EPA was fed in the sn-2 position of dietary TAG compared to the sn-1(3) position. In terms of murine macrophage function there was no effect of dietary DHA, while dietary EPA was found to dose-dependently decrease the number of macrophages performing phagocytosis. However, when EPA was fed in the sn-2 position there was an increase ability for active macrophages to engulf bacteria, while when fed in the sn-1(3) position this was not seen.

It is concluded that while long-chain n-3 PUFA, especially EPA, do possess immunomodulatory effects, modest increase in their consumption by healthy humans do not alter immune function as assessed in this study. This is despite significant changes in immune cell fatty acid composition.

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