Prostaglandin E 2 production and T cell function after fish-oil supplementation : response to antioxidant cosupplementation 1 – 3

Background: Prostaglandin E2 (PGE2) inhibits lymphocyte proliferation and the production of interferon(IFN) by peripheral blood mononuclear cells, but the effect of PGE2 on interleukin 4 (IL-4) production is unclear. Fish oil, which contains eicosapentaenoic and docosahexaenoic acids, inhibits production of PGE2. The effects of fish oil on lymphocyte proliferation and production of IFNand IL-4 are unclear and may be influenced by the availability of antioxidants. Objective: We investigated the effect of dietary fish oil with and without antioxidant cosupplementation on lymphocyte proliferation and the production of PGE2, IFN, and IL-4 by peripheral blood mononuclear cells. Design: Sixteen healthy men received dietary fish-oil supplements providing 0.3, 1, and 2 g eicosapentaenoic acid plus docosahexaenoic acid/d for 4 consecutive weeks each (total of 12 wk). All subjects were randomly assigned to daily cosupplementation with either antioxidants (200 g Se, 3 mg Mn, 30 mg RRR-tocopheryl succinate, 90 mg ascorbic acid, 450 g vitamin A) or placebo. Results: Fish-oil supplementation decreased PGE2 production and increased IFNproduction and lymphocyte proliferation from baseline values. Cosupplementation with antioxidants did not affect cytokine production or lymphocyte proliferation. Conclusion: Dietary fish oil modulates production of IFNand lymphocyte proliferation in a manner consistent with decreased production of PGE2, but this effect is not modified by antioxidant cosupplementation. Am J Clin Nutr 2003;78:376–82.

[1]  D. Peeters,et al.  Seasonal variation in peripheral blood leukocyte subsets and in serum interleukin-6, and soluble interleukin-2 and-6 receptor concentrations in normal volunteers , 1994, Experientia.

[2]  P. Calder,et al.  Dietary supplementation with gamma-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans. , 2001, The Journal of nutrition.

[3]  A. Brash.  Arachidonic acid as a bioactive molecule. , 2001, The Journal of clinical investigation.

[4]  S. Wootton,et al.  A method for separation of phosphatidylcholine, triacylglycerol, non-esterified fatty acids and cholesterol esters from plasma by solid-phase extraction* , 2000, British Journal of Nutrition.

[5]  P. Calder,et al.  Effect of low-to-moderate amounts of dietary fish oil on neutrophil lipid composition and function , 2000, Lipids.

[6]  R. Morris,et al.  Seasonal variation in interleukin 4 in patients with hayfever. , 2000, Cytokine.

[7]  Calder,et al.  Encapsulated fish oil enriched in α‐tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions , 2000, European journal of clinical investigation.

[8]  P. Calder,et al.  Comparison of cytokine production in cultures of whole human blood and purified mononuclear cells. , 1999, Cytokine.

[9]  S. Heys,et al.  Modulation in vitro of human natural cytotoxicity, lymphocyte proliferative response to mitogens and cytokine production by essential fatty acids , 1997, Immunology.

[10]  D. Brown,et al.  PGE2 regulation of B lymphocytes and T helper 1 and T helper 2 cells: induction of inflammatory versus allergic responses. , 1997, Advances in experimental medicine and biology.

[11]  M. Kapsenberg,et al.  Modulation of T-cell cytokine secretion by accessory cell-derived products. , 1996, The European respiratory journal. Supplement.

[12]  T. Mosmann,et al.  The expanding universe of T-cell subsets: Th1, Th2 and more. , 1996, Immunology today.

[13]  E. Schmidt,et al.  No effect of a very low dose of n-3 fatty acids on monocyte function in healthy humans. , 1996, Scandinavian journal of clinical and laboratory investigation.

[14]  Dayong Wu,et al.  Immunologic effects of marine- and plant-derived n-3 polyunsaturated fatty acids in nonhuman primates. , 1996, The American journal of clinical nutrition.

[15]  V. Gallai†,et al.  Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids , 1995, Journal of Neuroimmunology.

[16]  C. Dinarello,et al.  Dietary supplementation with n‐3 fatty acids suppresses interleukin‐2 production and mononuclear cell proliferation , 1993, Journal of leukocyte biology.

[17]  H. Rasmussen,et al.  Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived N-3 fatty acid enrichment. , 1993, The Journal of clinical investigation.

[18]  M. Gibney,et al.  The effects of short- and long-term supplementation with fish oil on the incorporation of n-3 polyunsaturated fatty acids into cells of the immune system in healthy volunteers. , 1993, European journal of clinical nutrition.

[19]  C. Drevon,et al.  Very long chain n‐3 and n‐6 polyunsaturated fatty acids inhibit proliferation of human T‐lymphocytes in vitro , 1993, European journal of clinical investigation.

[20]  P. Calder,et al.  Polyunsaturated fatty acids suppress human peripheral blood lymphocyte proliferation and interleukin-2 production. , 1992, Clinical science.

[21]  P. Calder,et al.  The inhibition of T-lymphocyte proliferation by fatty acids is via an eicosanoid-independent mechanism. , 1992, Immunology.

[22]  P. Calder,et al.  Unsaturated fatty acids suppress interleukin-2 production and transferrin receptor expression by concanavalin A-stimulated rat Iymphocytes , 1992, Mediators of inflammation.

[23]  P. Taylor,et al.  Increased vitamin E intake restores fish-oil-induced suppressed blastogenesis of mitogen-stimulated T lymphocytes. , 1991, American Journal of Clinical Nutrition.

[24]  F. Pociot,et al.  Dietary Supplementation with co‐3‐Polyunsaturated Fatty Acids Decreases Mononuclear Cell Proliferation and Interleukin‐1β Content but not Monokine Secretion in Healthy and Insulin‐Dependent Diabetic Individuals , 1991, Scandinavian journal of immunology.

[25]  B. Goldin,et al.  Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. , 1991, The Journal of nutrition.

[26]  Nancy C. Free,et al.  Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women. , 1991, The Journal of nutrition.

[27]  T. Saldeen,et al.  The effects of fish oil on triglycerides, cholesterol, fibrinogen and malondialdehyde in humans supplemented with vitamin E. , 1991, The Journal of nutrition.

[28]  M. Betz,et al.  Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. , 1991, Journal of immunology.

[29]  A. Donker,et al.  Dose-response effects of fish-oil supplementation in healthy volunteers. , 1990, The American journal of clinical nutrition.

[30]  H. Mcdevitt,et al.  Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[31]  D. Santoli,et al.  Prostaglandin E precursor fatty acids inhibit human IL-2 production by a prostaglandin E-independent mechanism. , 1989, Journal of immunology.

[32]  M. Goldyne.  Eicosanoid metabolism by lymphocytes: do all human nucleated cells generate eicosanoids? , 1989, Pharmacological research.

[33]  R. Messner,et al.  Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell , 1977, The Journal of experimental medicine.

[34]  J. Folch,et al.  A simple method for the isolation and purification of total lipides from animal tissues. , 1957, The Journal of biological chemistry.