EPA and DHA and acquired immune function

Animal studies

Studies in rabbits, chickens, rats and mice have clearly demonstrated that long-chain n-3 PUFAs can inhibit lymphocyte proliferation, IL-2 and interferon (IFN)-7 production, delayed-type hypersensitivity and antigen presentation, as compared with diets rich in lard, or hydrogenated coconut, safflower, maize or linseed oils (e.g. Fujikawa et al., 1992; Yaqoob et al., 1994b; Sanderson et al., 1995, 1997; Byleveld et al., 1999; Wallace et al., 2001).

The addition of either EPA or DHA to a diet was demonstrated to suppress T-cell proliferation in rats (Peterson et al., 1998) and mice (Jolly et al., 1997). Although mechanistically important, the physiological importance of many of the animal studies in this area is not clear, as the diets used to identify the effects of long-chain n-3 PUFAs often contain very high amounts of these fatty acids and very low amounts of linoleic acid. Indeed, in contrast to many other studies, adding EPA and DHA at 5% by weight in both a high- and low-PUFA diet improved rat lymphocyte responses, measured as activation-marker expression and cytokine production (Robinson and Field, 1998; Robinson et al., 2001).

Human studies

Human studies have generally provided less fish oil (as a proportion of fat or energy) in the diet than the amount fed in most studies in animals. Despite this, data from studies investigating the influence of fish oil on human lymphocyte functions are also conflicting. Supplementation of the diet of healthy human volunteers with fish oil providing 2.4 g EPA plus DHA day-1 resulted in decreased proliferation of lymphocytes from older women (aged 51-68 years) but not young women (aged 21-33 years) and decreased IL-2 production (Meydani et al., 1991). Molvig et al. (1991) reported decreased lymphocyte proliferation after providing 1.7 or 3.4 g EPA plus DHA day-1 to men, while Gallai et al. (1993) reported that 5.2 g EPA plus DHA day-1 decreased IL-2 and IFN-7 production. Providing 1.2 g EPA plus DHA to healthy subjects aged 55-75 years resulted in decreased lymphocyte proliferation (Thies et al., 2001c), but did not affect IL-2 or IFN-7 production (Thies et al., 2001c). Inclusion of oily fish providing 1.2 g EPA plus DHA day-1 in the diet of volunteers consuming a low-fat, low-cholesterol diet decreased lymphocyte proliferation, IL-2 production and the delayed-type hypersensitivity response to seven recall antigens (Meydani et al., 1993). In contrast to these observations, there are reports of no effect of 3.2 g EPA plus DHA day-1 on lymphocyte proliferation and IL-2 and IFN-7 production (Yaqoob et al., 2000) by peripheral-blood lymphocytes and of no effect of 4.6 g EPA plus DHA day-1 on lymphocyte proliferation and IL-2 production (Endres et al., 1993). Thus, feeding moderate amounts of long-chain n-3 PUFAs is not clearly immunosuppressive, although feeding high amounts might be.

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