N-3 polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes and inhibit antigen presentation in vitro

Abstract

SUMMARYN-3 polyunsaturated fatty acid (PUFA)-rich diets are associated with suppression of cell-mediated immune responses, but the mechanisms are unclear. Specific immune responses are initiated by antigenpresenting cells (APC). We have previously shown in vitro that the n-3 PUFA, eicosapentaenoic acid (EPA), inhibits the expression of HLA-DR, an MHC class II molecule required for normal APC function on human blood monocytes. In contrast, docosahexaenoic acid (DHA) enhanced the expression of this molecule on unstimulated monocytes, but both n-3 PUFA suppressed its expression on interferongamma (IFN-g)-activated monocytes. In the present study we show that when EPA and DHA were combined at the same ratio as is commonly found in fish oil supplement capsules (3:2) there was no significant effect in vitro on the expression of HLA-DR on unstimulated monocytes, but the expression on IFN-g-activated monocytes remained significantly inhibited. In the same in vitro system a significant reduction in the ability of IFN-g-activated monocytes to present tetanus toxoid antigen to autologous lymphocytes was observed following culture with the combined n-3 PUFA. These findings support previous animal studies which suggest that n-3 PUFA can inhibit the antigen-presenting function of mononuclear phagocytes.

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

“…Still other studies have shown that linoleic acid (n-6) decreases the activity of IL-2 [129], and increases IL-1 production and tissue response to cytokines, while n-3 generally decreases IL-1 production and activity [44]. Despite some disagreement among studies, it seems that n-3 fatty acids (alpha-linolenic acid, DHA, EPA) decrease the production and activity of the pro-inflammatory cytokines (IL-1, IL-6, TNF alpha ) [13,20,52,124] and that n-6 family has the opposite effect [19,44,54]. The ability of n-3 PUFA to reduce pro-inflammatory cytokines and prostaglandin [21] lead to the proposal for the use of fish oil to relieve pain.…”

Effect of fatty acids on leukocyte function

“…It has been found that monocytes treated with eicosapentaenoic acid (EPA) have lower expression of ICAM-1, an effect that is opposite to that of docosahexaenoic acid (DHA) (5). After monocyte stimulation, it has been found that both EPA and DHA (omega-3 fatty acids) had a reduced expression of ICAM-1 (5).…”

“…Monocytes from animals fed diets rich in omega-3 fatty acids (fish oil) have lower antigen-presenting capability (5), that may be associated with a decreased expression of major histocompatibility complex II (MHC II) molecules on macrophages, which are essential for antigen presentation to lymphocytes (5). PUFAs, especially DHA, can inhibit the expression of these molecules in INF-gamma-stimulated cells.…”

“…Macrophages and neutrophils -Fatty acid-fed animals show decreased cell activation, production of reactive oxygen species (ROS), phagocytosis and antigen presentation (by macrophages) (5,(13)(14)(15)19,21,28). -The addition of fatty acids to the cell medium increases ROS formation and phagocytosis (12,15,20).…”

The effects of dietary lipids on gene expression and apoptosis

“…While the majority of these studies have taken place in mice, similar effects have been found also in human subjects. For example, dietary FO suppressed the ability of macrophages to present antigen to T lymphocytes (Hughes et al 1997). T lymphocyte IL-2 secretion and subsequent proliferation was significantly suppressed by FO supplementation in human subjects (Endres et al 1993).…”