Influence of n-3 polyunsaturated fatty acids (PUFA) on the antigen-presenting function of human monocytes.

Abstract

N-3 polyunsaturated fatty acid (PUFA)-rich diets are associated with suppression of cell mediated immune responses and there is growing interest in the potential use of dietary fish oil [rich in the n3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid @HA)] supplementation in the treatment of disorders involving an overreactive immune response, such as rheumatoid arthritis [see 1 for review]. Specific immune responses are initiated by the presentation of antigen to helper T-lymphocytes on the surface of an antigen-presenting cell (APC). A pre-requisite for this function of APCs is the cell surface expression of major histocompatibility complex (MHC) class I1 molecules (HLA-DR, -DP and D Q , aided by the presence of adhesion molecules. It has been shown that the percentage of MHC class 11-positive monocytes and the density of these molecules on the cell surface can alter the degree of immune responsiveness of an individual [2]. We have previously shown in vitro that EPA can inhibit the expression of the MHC class I1 molecule HLA-DR and of the adhesion molecule ICAM-1 on both unstimulated monocytes and on interferon-gamma (IFN-g) activated human monocytes [3]. In conaast, DHA increased the expression of these surface molecules on unstimulated monocytes, although it inhibited their expression on IFN-g stimulated cells in a similar manner to EPA [3]. In a dietary study, we observed a reduction in the relative number of HLA-DR and ICAM-1 molecules expressed on human peripheral blood monocytes following 3 weeks of fish oil supplementation [4]. Since most commercially available fish oil supplements contain a mixture of EPA and DHA, we undertook further in virro experiments to determine the combined effect of these n-3 PUFA on the cell surface expression of surface molecules involved in the process of antigen-presentation. In addition, the antigen-presenting function of monocytes, following incubation with or without n-3 PUFA, was assessed using tetanus toxoid as a challenge antigen. Purified monocytes, obtained from healthy volunteers, were incubated with or without a mixture of EPA and DHA (final total concentration 20 pg/ml, combined at the same ratio as is commonly found in fish oil supplement capsules, ie. 2:l) in RPMI culture medium supplemented with 5% fetal calf serum for 48 h at 37'C. In addition, parallel cultures were performed in the presence of IFN-g (400 U/ml) to stimulate upregulation of MHC class I1 molecule expression by the monocytes.