Polyunsaturated fatty acids and allergy development

Sammanfattning: Allergies have increased strikingly in the affluent parts of the world during the last century. The cause of the rapid increase is unknown but several risk factors have been postulated, the main ones relating to reduced microbial exposures and changed diet. In parallel with the increased prevalence of allergies, consumption of saturated fat has declined, while consumption of polyunsaturated fat has risen. The change in dietary fatty acid composition is suggested to influence the risk of developing allergy. This thesis work aimed to investigate whether and how the fatty acid compositions in the body and in the diet affect allergy development. The fatty acid pattern in breast milk and serum was investigated in women with different allergic manifestations. Furthermore, the fatty acid pattern in cord blood was analyzed as a putative factor affecting subsequent development of allergies. In animal models, the effect of diets rich in polyunsaturated fatty acids (PUFAs) on different types of immune responses and hypersensitivity reactions was studied and the consumption of PUFAs during allergic reactions was evaluated. Since dairy farms are known to be an allergy-preventing environment, dietary differences between farmers and non-farmers were investigated. Lactating women with an allergic phenotype that included eczema had PUFA patterns in breast milk and serum that differed from that of non-allergic women and women with respiratory allergies. Eczematous women had lower levels of several PUFAs, such as arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), compared to non-allergic women as well as women with isolated respiratory allergy. Fatty acid pattern in cord blood was measured in children that subsequently developed eczema or respiratory allergies. Infants who later developed allergies had higher cord blood levels of PUFAs, both from the n-3 and n-6 series, than children who stayed non-allergic. Studies in mouse models showed that a diet rich in n-3 PUFA (supplemented with fish oil) increased IgE production in an airway hypersensitivity model, but suppressed proliferation and cytokine production of T cells in a delayed-type hypersensitivity (DTH) model. During the challenge phase and the resulting allergic inflammatory reaction a significant reduction of PUFAs was monitored in both models, but most obvious in the airway model. When comparing farming and non-farming women, farmers had higher levels of saturated fatty acids (SAFAs) and lower levels of PUFAs in their breast milk. Farmers also had a higher intake of foods containing SAFAs, such as butter and whole-fat dairy products. Conversely, non-farmers had a higher intake of PUFA-rich margarine and low-fat dairy products. In conclusion, fatty acid pattern in the body and fatty acid composition in the diet are associated with allergy development. Dietary intake of both n-3 and n-6 PUFAs appear to facilitate atopic sensitization and allergy development in both a prospective birth-cohort study and in an experimental allergy model. The PUFAs are then consumed in the body during the allergic inflammatory reaction, which may explain the low PUFA levels characterizing allergic subjects. Thus, high intake of PUFAs may predispose to allergy and a diet rich in saturated fatty acids and low in PUFAs may be one factor explaining the low allergy prevalence among children growing up on dairy farms.