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Dietary n6 and n-3 fatty acids in immunity and autoimmune disease

Lipid biology plays a significant role in the normal and pathological functioning of cells of the immune system (Hopkins et al. 1981; Dvorak et al. 1983; Schlager et al. 1983; Shipman et al. 1988; Roper et al. 1990; Goetzl et al. 1995; Pushkareva et al. 1995; Hennig et al. 1996). In addition to the physiological requirements of cells of the immune system for essential fatty acids, dietary fatty acid modulation of the membrane composition and functions of immune cells can affect both normal and pathological processes (Calder, 1996; Harbige, 1996; Hennig et al. 1996). Among the first immunologists to recognize the importance of dietary fatty acids in immunity and autoimmune disease were Peter Medawar and Jiirgen Mertin (Medawar et al. 1979) in the UK and Gabriel Fernandes and Robert Good (Fernandes et al. 1972) in the USA. The importance of dietary fatty acids in the prevention or control of autoimmune disease in animal models is now well documented (Mertin, 1981; Levy et al. 1982; Kelley et al. 1985; MOKOW et al. 1985; Robinson et al. 1986; Alexander et al. 1987; Harbige et al. 1995; Lin et al. 1996). However, the biochemical and immunological mechanisms by which dietary fatty acids affect the immune system and autoimmunity have remained largely obscure. In recent years important new concepts in immunoregulation have emerged which are likely to be of significance to effects of fatty acid nutrition on immunity. Mosman & Coffman (1989) have characterized two different patterns of cytokine secretion by T-cells which lead to different functional responses. T helper1 (Thl) cells produce interleulun (1L)-2, interferon-y and tumour necrosis factor-p which are not synthesized by Th2 cells. In contrast, Th2 cells (but not Thl) produce IL-4, IL-5 and IL-10. Thl cells enhance cell-mediated inflammatory activity, whereas T h 2 cells synthesize cytokines that help B-cells develop into antibody-producing cells. There are also T-cells able to produce both Thl and T h 2 cytokines, referred to as Tho cells (Male et al. 1996). Weiner (1997) has further characterized a T h 3 T-cell subset that primarily produces transforming growth factor4 (TGV), provides help for immunoglobulin (Ig) A production, and has suppressive properties. Importantly, the overall balance of cytokine production by Thl, Th2, and T h 3 cells affects the type of immune response generated, e.g. Th2 cytokines can down-regulate production of Thl cytokines and vice versa (Male et al. 1996). Eicosanoids are known to affect these immunoregulatory mechanisms (Phipps et al. 1991), which may, in part, explain the complex relationship between the immune system, eicosanoids and the eicosanoid precursor polyunsaturated fatty acids derived from the diet. The balance of membrane fatty acids and eicosanoids is also known to influence inflammatory reactions (Terano et al. 1984; Lefkowith, 1988; Tate etal. 1989; Ross, 1993; Calder, 1996; Hennig et al. 1996).