Effect of docosahexaenoic acid-rich fish oil supplementation on human leukocyte function.

BACKGROUND: The effect of a docosahexaenoic acid (DHA)-rich fish oil (FO) supplementation on human leukocyte function was investigated. METHODS: Ten male volunteers were supplemented with 3g/day FO containing 26% eicosapentaenoic acid (EPA, 20:5, n-3) and 54% DHA (22:6, n-3) for 2 months. RESULTS: FO supplementation changed the fatty acid (FA) composition of leukocytes resulting in an increase of n-3/n-6 ratio from 0.18 to 0.62 in lymphocytes and from 0.15 to 0.70 in neutrophils. DHA-rich FO stimulated an increase in phagocytic activity by 62% and 145% in neutrophils and monocytes, respectively. Neutrophil chemotactic response was increased by 128%. The rate of production of reactive oxygen species by neutrophils was also increased, as it was with lymphocyte proliferation. These changes were partially reversed after a 2-month wash out period. With respect to cytokine production by lymphocytes, interleukin (IL)-4 release was not altered, whereas secretions of IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were raised. These results are in contrast to those described by others using EPA-rich FO supplementation. Lymphocyte pleiotropic gene expression was analyzed by a macroarray technique. Of the analyzed genes (588 in total), 77 were modified by the supplementation. FO supplementation resulted in up-regulation of 6 genes (GATA binding protein 2, IL-6 signal transducer, transforming growth factor alpha, TNF, heat shock 90kDa protein 1-alpha and heat shock protein 70kDa 1A) and a down regulation of 71 genes (92.2% of total genes changed). The largest functional group of altered genes was that related to signaling pathways (22% of the total modified genes). CONCLUSIONS: Therefore, although EPA and DHA are members of n-3 FA family, changes in the proportion of DHA and EPA exert different effects on neutrophil, monocyte and lymphocyte function, which may be a result of specific changes in gene expression.

Comparative effects of eicosapentaenoic acid and docosahexaenoic acid on proliferation, cytokine production, and pleiotropic gene expression in Jurkat cells.

Comparative effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) acid on Jurkat T cells were investigated. The following parameters were evaluated: concanavalin A (Con A) induced proliferation, production of interleukin-2 (IL-2), IL-4, IL-10, and interferon-gamma (INF-gamma), and expression of pleiotropic genes by macroarray technique (83 genes in total). DHA inhibiting effect on Con A-induced proliferation was more pronounced than that of EPA. The decrease in IL-2 and INF-gamma production was observed for both fatty acids, whereas the production of IL-10 was decreased by EPA only. The expression of a significant proportion of genes was altered by the fatty acids; 30% for DHA (25 genes) and 26.5% for EPA (22 genes). DHA and EPA markedly affected the expression of genes clustered as cytokines and related receptors, signal transduction pathways, transcription factors, cell cycle, defense and repair, apoptosis, DNA synthesis, cell adhesion, cytoskeleton, and hormone receptors. Therefore, the effect of fatty acids on T-lymphocyte function involves regulation of expression of important genes. Marked differences were observed between the effects of EPA and DHA, indicating that it is an over-simplification to generalize the effects of n-3 fatty acids.

Effects of EPA and DHA on proliferation, cytokine production, and gene expression in Raji cells.

The effects of EPA and DHA on the function and gene expression of a B-lymphocyte cell line (Raji) were investigated. Proliferation; production of interleukin-10 (IL-10), tumor necrosis factor (TNF)-alpha, and interferon (INF)-gamma; and expression of pleiotropic genes were evaluated. Cell proliferation was increased in the presence of 12.5 microM EPA (approximately twofold) and 12.5 microM DHA (approximately 1.5-fold). EPA and DHA (25 microM) also decreased production of the key immunoregulatory cytokines IL-10, TNF-alpha, and INF-gamma. EPA and DHA changed the expression of specific genes, but this effect was more marked for EPA (25.9% of genes investigated) compared with DHA (8.4% of genes investigated). EPA and DHA affected the expression of genes clustered as: cytokines, signal transduction, transcription, cell cycle, defense and repair, apoptosis, cell adhesion, cytoskeleton, and hormones. The most remarkable changes were observed in the genes of signal transduction and transcription. These results led us to conclude that the mechanism of DHA and EPA effects on B-lymphocyte functions includes regulation of gene expression. Thus, the ingestion of fish oil, a rich source of EPA and DHA, may have a strong effect on B-lymphocyte function in vivo. However, remarkable differences were observed between DHA and EPA, demonstrating that specific effects of these FA may be responsible for the marked differences in edible oil effects on immune function in vivo reported by others.