Modulation in vitro of human natural cytotoxicity, lymphocyte proliferative response to mitogens and cytokine production by essential fatty acids

Abstract

SUMMARYEssential fatty acids ( EFA) have been shown in animal studies to have a differential effect on various aspects of immune reactivity. However, there have been few studies in humans. Therefore, we elected to investigate the effects of a variety of EFA [gamma-linolenic acid (GLA), eicosapentaenoic acid ( EPA) and docosahexaenoic acid (DHA)] in vitro on human blood lymphocyte reactivity, cytokine secretion and natural cytotoxicity. The proliferative response to polyclonal mitogens (phytohaemagglutinin, pokeweed mitogen, concanavalin A), as measured by [3H]thymidine incorporation into newly synthesized lymphocytes, was inhibited (P<0·05) by all EFAs tested, in a dose-dependent manner (3-15 mg/ml ). The greatest inhibition of proliferation was caused by EPA and DHA. Similarly, EPA, DHA and GLA significantly reduced cytotoxic activity [expressed as lytic units, using 51 chromium-release assays, natural killer ( NK) ( K562 cells) and lymphokine-activated (LAK ) (Daudi cells) cells] (P<0·05) in a concentration-dependent manner ( 5-50 mg/ml ), without affecting cell viability. EPA and DHA exhibited greater suppression than GLA. Furthermore, the inhibition of cell proliferation and suppression of natural cytotoxicity was associated with marked decrease in cytokine [interleukin-1 (IL-1), IL-2, tumour necrosis factor-a ( TNF-a) and interferon-c ( IFN-c)] production in vitro. Our findings demonstrate that EFAs (GLA, EPA, DHA) have the potential to inhibit significantly various aspects of human lymphocyte cell-mediated and humoral immune reactivities.

Depression and long chain n-3 fatty acids in adipose tissue in adults from Crete

“…Specifically, in vitro studies have shown that EPA and DHA suppress IL-6 production by human endothelial cells (Khalfoun et al, 1997). EPA and DHA have been reported to suppress the in vitro production of IL-1, IL-2, IL-6, TNF-a and INF-g by human lymphocytes (Purasiri et al, 1997). Human studies have indicated that dietary supplementation with EPA and DHA results in suppression of IL-1, IL-2, IL-6 and TNF-a production by monocytes (Calder, 1997).…”

Effect of fatty acids on leukocyte function

“…Gamma-linolenic acid reduces IL-1beta secretion by monocytes (22). Other authors (23,24) have found that omega-6 PUFAs generally raise IL-1 production and that omega-3 PUFAs have the opposite effect.…”

“…On the other hand, human neutrophils treated with omega-3 fatty acids show decreased production of IFN-gamma (24).…”

“…The same authors have shown that other saturated fatty acids are more potent than unsaturated fatty acids in modulating cytokine production, particularly in relation to IFNgamma. Lymphocytes treated with omega-3 fatty acids as well as with butyrate show decreased IFN-gamma production (24,39).…”

“…Thus, dihomogamma-linoleic acid and arachidonic acid inhibit the production of IL-2 by lymphocytes, an effect that cannot be abolished by cyclooxygenase inhibitors. Most PUFAs can decrease IL-2 production, particularly of the omega-3 class, and EPA has the highest potency among them, an effect associated with their inhibitory action on lymphocyte proliferation and with lowered expression of IL-2 receptor, with a decrease in naive T cells and a rise in memory T cells (3,24).…”