Dietary fatty acids affect inflammatory mediator production by mirine and human macrophages and lymphocytes

Abstract

The purpose of the experiments presented in this thesis is to clarify the effects of dietary n-3 fatty acids on the production of inflammatory mediators by cells of the murine and human immune systems. The mouse studies involved feeding diets containing different types of fatty acids for 8-12 weeks and investigated lymphocyte profileration in response to mitogenic stimulation, the ability of macrophages to kill target cell lines and the production of inflammatory mediators, including cytokines, by stimulated macrophages. These studies found that the type of fatty acid eaten in the diet affects the fatty acid composition of mouse macrophages and lymphocytes and this in turn had an effect on the ability of these cells to produce some inflammatory mediators, including prostaglandin E₂, leukotriene B₄, tumour necrosis factor-α, interleukin-1β, and interleukin-6. The exact effects of dietary fatty acid manipulation on inflammatory mediator production by macrophages were dependent on the activation state of the macrophage under investigation. In addition, dietary fatty acid manipulation had an effect on the ability of macrophages to kill target tumour cells. The studies in humans involved supplementing the diet of healthy men aged 18-40 years for three months with increasing doses of n-3 fatty acid-rich fish oil (3, 6 or 9 g/fish oil per day), linseed oil, or a placebo oil containing a mix of fatty acids found in the typical UK diet. Supplementation of the diet with fish oil caused significant increases in the proportions of n-3 fatty acids present in plasma phospholipids. There were also some changes in the proportions of n-3 fatty acids present in circulating mononuclear cells. Supplementation of the diet with 6 and 9 g fish oil per day for three months caused a significant decrease in the ability of mononuclear cells to produce interleukin-6 and prostaglandin-E₂ upon stimulation. The research presented in this thesis provides information crucial to underpin the use of fatty acids as a nutritional means of modulating the immune response.

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