Docosahexaenoic and Eicosapentaenoic Acids Inhibit Human Lymphoproliferative Responses In Vitro but not the Expression of T Cell Surface Activation Markers

Abstract

The effects of polyunsaturated fatty acids (PUFAs: docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids) on induced lymphocyte proliferation and expression of CD25alpha chain of interleukin-2 receptor, CD71 and HLA-DR were investigated. PUFAs had no effect on phytohaemagglutinin (PHA)-induced lymphocyte agglutination, but they strongly inhibited the lymphoproliferative response to PHA. This inhibitory effect is PUFA dose-dependent and seems to be more potent with DHA than EPA, Pre-incubation experiments showed that lymphocytes cultured with PUFAs for 6 h then washed and exposed to PHA, still inhibited lymphocyte proliferation. The authors also showed that this inhibitory activity was time dependent but became nonsignificant when PUFAs were added after 48 h lymphocyte culture. The addition of excess exogenous human recombinant rIL-2 partly restored PHA-lymphocyte proliferation inhibited by EPA but not by DHA. On the other hand, the authors showed that PUFAS did not inhibit IL-2 stimulated lymphocyte proliferation. The addition of PUFAs to cell culture medium had no inhibitory action on the PHA-induced lymphocyte expression of CD25, CD71 and HLA-DR. Furthermore, this effect appeared independent of eicosanoid synthesis or peroxide formation. Indeed, the inclusion of aspirin and vitamin E in the culture medium did not prevent the inhibitory effects of PUFAs on lymphocyte proliferation. Regardless of the mechanism of action, the inhibitory effect of PUFAs on activated lymphocytes may explain why some clinical trials of fish oil supplemented diets containing high amounts of DHA and EPA have been successful in improving the health status of patients suffering from inflammatory and autoimmune disorders.

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

“…Thus, differences in PGE 2 production cannot be responsible for the differences in lymphocyte proliferation observed. This agrees with the outcomes of a number of in vitro studies which have concluded that the inhibitory effects of EPA and DHA upon lymphocyte proliferation are independent of their effects upon PGE 2 production (59)(60)(61)(62). There is also agreement with studies in humans in which supplementation of the diet with fish oil has been shown to reduce both lymphocyte proliferation and PGE 2 production (50,51); these studies concluded that the effect of n-3 fatty acid supplementation on lymphocyte proliferation seems independent of, and is unlikely due to, decreases in PGE 2 production (50,51).…”

Dietary fatty acids and lymphocyte functions

“…Recent studies have confirmed that y-linolenic, eicosapentaenoic and docosahexaenoic acids inhibit mitogenstimulated lymphocyte proliferation (Khalfoun et al 1996b;Purasiri et al 1997). The inhibition of lymphocyte proliferation by unsaturated fatty acids is not prevented by inhibitors of phospholipase A2 (EC 3.1.1.4), cyclooxygenase (EC 1.14.99.1) or lipoxygenase (EC 1.…”

“…The inhibition of lymphocyte proliferation by unsaturated fatty acids is not prevented by inhibitors of phospholipase A2 (EC 3.1.1.4), cyclooxygenase (EC 1.14.99.1) or lipoxygenase (EC 1. 13.11.12;Santoli et al 1990;Calder et al 1992;Kumar et al 1992;Soyland et al 1993;Rotondo et al 1994;Khalfoun et al 1996b), suggesting that the effects of the fatty acids are independent of eicosanoid synthesis. Furthermore, the inhibition of proliferation by unsaturated fatty acids is not prevented by a-tocopherol and other antioxidants (Calder & Newsholme, 1993;Soyland et al 1993;Khalfoun et al 1996b), suggesting that the effects of the fatty acids are independent of lipid peroxidation.…”

<i>FADS</i> Gene Cluster Polymorphisms: Important Modulators of Fatty Acid Levels and Their Impact on Atopic Diseases

“…Arachidonic acid is one of the main precursors of prostaglandins and leukotrienes [51] and activates allergic immune responses via its products, prostaglandin E2 and leukotriene B4 [52][53][54][55][56] . For -3 fatty acids like eicosapentaenoic acid and docosahexaenoic acid, modulation of cytokine responses has also been shown [57] , whereas dietary treatment with these -3 fatty acids in inflammatory disorders suggests rather anti-inflammatory properties in contrast to the products of arachidonic acid [58] . One reason for the proposed defect in enzyme activity of the ⌬ 6 desaturase, possibly leading to an imbalance between -6 and -3 LC-PUFAs and therefore to disturbed inflammatory processes, could be mutations or polymorphisms in the ⌬ 6 desaturase encoding the FADS2 gene.…”