Dietary polyunsaturated fatty acids and inflammatory mediator production

Many antiinflammatory pharmaceutical products inhibit the production of cer tain eicosanoids and cytokines and it is here that possibilities exist for therapies that incorporate n-3 and n-9 dietary fatty acids. The proinflamma tory eicosanoids prostaglandin E-2 (PGE(2)) and leukotriene B-4 (LTB4) are derived from the n-6 fatty acid arachidonic acid (AA), which is maintained at high cellular concentrations by the high n-6 and low n-3 polyunsaturated fatty acid content of the modern Western diet. Flaxseed oil contains the 1 8-carbon n-3 fatty acid alpha-linolenic acid, which can be converted after ingestion to the 20-carbon n-3 fatty acid eicosapentaenoic acid (EPA). Fish oils contain both 20- and 22-carbon n-3 fatty acids, EPA and docosahexaeno ic acid. EPA can act as a competitive inhibitor of AA conversion to PGE(2) and LTB4, and decreased synthesis of one or both of these eicosanoids has b een observed after inclusion of flaxseed oil or fish oil in the diet. Analo gous to the effect of n-3 fatty acids, inclusion of the 20-carbon n-9 fatty acid eicosatrienoic acid in the diet also results in decreased synthesis o f LTB4. Regarding the proinflammatory cytokines, tumor necrosis factor alph a and interleukin 1 beta, studies of healthy volunteers and rheumatoid arth ritis patients have shown less than or equal to 90% inhibition of cytokine production after dietary supplementation with fish oil. Use of flaxseed oil in domestic food preparation also reduced production of these cytokines. N ovel antiinflammatory therapies can be developed that take advantage of pos itive interactions between the dietary fats and existing or newly developed pharmaceutical products.