Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E₂production but have different effects on lymphocyte functions and cell‐mediated immunity

Abstract

Weanling rats were fed on high-fat (178 g/kg) diets which contained 4.4 g alpha-linolenic (ALA), gamma-linolenic, arachidonic (ARA), eicosapentaenoic (EPA), or docosahexaenoic acid (DHA)/100 g total fatty acids. The proportions of all other fatty acids, apart from linoleic acid, and the proportion of total polyunsaturated fatty acids (PUFA) (approximately 35 g/100 g total fatty acids) were constant, and the n-6 to n-3 PUFA ratio was maintained as close to 7 as possible. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Prostaglandin E2 production was enhanced from leukocytes from rats fed the ARA-rich diet and was decreased from leukocytes from the EPA- or DHA-fed rats. Replacing dietary ALA with EPA resulted in diminished ex vivo lymphocyte proliferation and natural killer (NK) cell activity and a reduced cell-mediated immune response in vivo. In contrast, replacing ALA with DHA reduced ex vivo lymphocyte proliferation but did not affect ex vivo NK cell activity or the cell-mediated immune response in vivo. Replacement of a proportion of linoleic acid with either gamma-linolenic acid or ARA did not affect lymphocyte proliferation, NK cell activity, or the cell-mediated immune response. Thus, this study shows that different n-3 PUFA exert different immunomodulatory actions, that EPA exerts more widespread and/or stronger immunomodulatory effects than DHA, that a low level of EPA is sufficient to influence the immune response, and that the immunomodulatory effects of fish oil may be mainly due to EPA.

n-3 Fatty acids and cardiovascular disease: Actions and molecular mechanisms

“…Thies et al [86] found that a moderate amount of EPA, but not other n-6 or n-3 FA can decrease NK cell activity in healthy subjects (>55 years). Peterson et al reported similar findings in rat spleen NK cell activity [87]. Other studies showed that increased intakes of EPA can decrease T lymphocyte functions such as proliferation and interleukin 2 productions in certain populations [88].…”

The effects of dietary lipids on gene expression and apoptosis

“…After 4 years, 40 % of the patients in the placebo group either died or had end-stage renal disease, whereas only 10 % of the patients in the FO group showed progression of disease. It appears that purified FO with antioxidant supplements may inhibit or delay the progression of renal disease by altering the production of pro-inflammatory cytokines, growth factors, and PG, perhaps decreasing activation and localization of complement, which may suppress deposition of antigen-antibody complexes in glomeruli (DeCaterina et al 1993(DeCaterina et al , 1994Gentile et al 1993;Nordkild et al 1993;Donadio et al 1994;Lin, 1994;Morphake et al 1994;Petterson et al 1994).…”

“…The classic effect of feeding FO is a decrease in the n-6 fatty acid arachidonic acid and concomitant increase in the n-3 fatty acids EPA and DHA in splenic lymphocyte membrane lipids. This effect is observed whether 100 g FOkg diet is fed to lupus-prone mice (Fernandes, 1994), 10 g EPA or DHA ethyl esterskg diet are fed to healthy mice (Hosack-Fowler et al 19938) or highly-purified EPA and DHA are given to rats (Peterson et al 1998). Once incorporated into immune cell phospholipids, n-3 fatty acids can affect a vast array of intracellular signalling pathways leading to altered gene expression.…”

“…Generally, integral membrane enzymes are up-regulated with increasing fluidity, while the activity of peripherally-associated enzymes may be down-regulated due to the less stable association with the membrane. Recently, it was found that dietary FO decreased phospholipase C-yl activity in activated lymphocytes (Peterson et al 1998). Thus, it appears that dietary FO may modulate events proximal to phospholipase activation (i.e.…”

The impact of omega-3 fatty acids on lung histopathology in mice model of chronic asthma

“…In addition, EPA and DHA are substrates for cyclooxygenase and lipoxygenase and give rise to mediators that often have different biological actions or potencies than those formed from AA (James et al, 2000, Calder, 2001. A couple of animal studies indicate that fish oil can have potent effects on immune function and inflammatory cell responses (Jolly et al, 1997;Peterson et al, 1998aPeterson et al, , 1998b.…”