Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation.

BACKGROUND Prostaglandin E(2) (PGE(2)) inhibits lymphocyte proliferation and the production of interferon-gamma (IFN-gamma) by peripheral blood mononuclear cells, but the effect of PGE(2) on interleukin 4 (IL-4) production is unclear. Fish oil, which contains eicosapentaenoic and docosahexaenoic acids, inhibits production of PGE(2). The effects of fish oil on lymphocyte proliferation and production of IFN-gamma and 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 PGE(2), IFN-gamma, 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 microg Se, 3 mg Mn, 30 mg RRR-alpha-tocopheryl succinate, 90 mg ascorbic acid, 450 micro g vitamin A) or placebo. RESULTS Fish-oil supplementation decreased PGE(2) production and increased IFN-gamma production and lymphocyte proliferation from baseline values. Cosupplementation with antioxidants did not affect cytokine production or lymphocyte proliferation. CONCLUSION Dietary fish oil modulates production of IFN-gamma and lymphocyte proliferation in a manner consistent with decreased production of PGE(2), but this effect is not modified by antioxidant cosupplementation.

[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]  J. Sterne,et al.  Dietary antioxidants and asthma in adults: population-based case-control study. , 2001, American journal of respiratory and critical care medicine.

[3]  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.

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

[5]  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.

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

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

[8]  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.

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

[10]  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.

[11]  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.

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

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

[14]  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.

[15]  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.

[16]  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.

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

[18]  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.

[19]  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.

[20]  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.

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

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

[23]  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.

[24]  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.

[25]  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.

[26]  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.

[27]  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.

[28]  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.

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

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

[31]  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.

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

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

[34]  P. Weber,et al.  The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. , 1989, The New England journal of medicine.

[35]  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.

[36]  W. J. Hadden,et al.  A Comparison of , 1971 .

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