Immunoregulation by Parenteral Lipids: Impact of the n-3 to n-6 Fatty Acid Ratio

Abstract

Background: The immune system is reported to be influenced by polyunsaturated fatty acids. Therefore, immunoregulation caused by intravenous fat emulsions with different n-3 to n-6 fatty acid ratios was studied in an in vivo model. Methods: Experimental rat heart allotransplantation served as a defined immunologic challenge. Twenty percent emulsions of safflower oil (n-3 to n-6 = 1:370), fish oil (n-3 to n-6 = 7.6:1), and soybean oil (n-3 to n-6 = 1:6.5), and a 1:1 mixture of safflower oil and fish oil (n-3 to n-6 = 1:2.1) were continuously infused (9 g of fat per kg of body weight per day) after transplantation until complete rejection. The prolongation of graft survival, an accepted parameter of immunosuppression, was assessed. Beyond that, cytokine release by mitogen-stimulated peripheral-blood mononuclear cells (PBMCs) from animals exsanguinated on day 4 after transplantation was evaluated. Results: The mean rejection time was 7.8 days in the sham-infused saline control group and 6.7 days in the safflower- and fish-oil-mixture group (oil control group). Continuous infusion of soybean oil prolonged the graft survival time to 10.4 days, fish oil to 12.3 days, and safflower oil to 13.3 days. PBMC α-tumor necrosis factor release was significantly reduced in the fish-oil group (51.9 ± 13.0 pg/106 PBMCs vs 70.8 ± 10.9 pg/106 PBMCs [controls], p < .004). Interleukin-6 release was diminished in both the fish-oil group (22.2 ± 13.6 pg/10⁶ PBMCs vs 40.7 ± 8.3 pg/106 PBMCs [controls], p < .002) and the safflower-oil group (28.4 ± 6.9 pg/10⁶ PBMCs, p < .002). Conclusions: The n-3 to n-6 fatty acid ratio determined the immunoregulatory potential of intravenous fat emulsions in vivo. Both n-3 and n-6 fatty acids were immunosuppressive when applied as the main polyunsaturated fatty acid sources. PBMC cytokine release was significantly reduced in these groups. The more balanced the n-3 to n-6 ratios, the less immunosuppressive the fat emulsion. There was no immunosuppressive effect at an n-3 to n-6 ratio of 1:2.1. (journal of Parenteral and Enteral Nutrition 18:417-421, 1994)

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References

Berken A. , Benacerraf B. : Depression of reticuloendothelial system phagocytic function by ingested lipids . Proc Soc Exp Biol 128:793-795. 1968

Meade CJ , Mertin J. : The mechanism of immunoinhibition by arachidonic and linoleic acid: Effects on the lymphoid and reticuloendothelial systems. Int Arch Allergy Appl Immunol 51:2-24, 1976

Perez RV , Waymack JP , Munda R. , et al: The effect of donor specific transfusions and dietary fatty acids on rat cardiac allograft survival. J Surg Res 42:335-340, 1987

Tchervenkov JI , Epstein MD , Alexander JW , et al: The effect of donor-specific blood transfusion, cyclosporine and dietary prostaglandin precursors on rat cardiac allograft survival. Transplantation 47,1:177-181, 1989

Otto DA , Kahn DR , Kahn MW , et al: Improved survival of heterotopic cardiac allografts in rats with dietary n-3 polyunsaturated fatty acids. Transplantation 50,2:193, 1990

Imagawa DK , Millis JM , Olthoff KM : The role of tumor necrosis factor in allograft rejection. II. Evidence that antibody therapy against tumor necrosis factor-alpha and lymphotoxin enhances cardiac allograft survival in rats. Transplantation 50,2:189-193-198, 1990

Muraguchi A. , Hirano T. , Tang B. , et al: The essential role of B-cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B-cells. J Exp Med 167:332-344, 1988

Weeks JR : Long term intravenous infusion. IN Methods in Psycho-biology , Meyers RD (ed). Academic Press, New York , 1972, p 155-171

Heron I. : A technique for accessory cervical heart transplantation in rabbits and rats . Acta Pathol Microbio Immunol Scand 79:366-372, 1973

10.

Kinsella JE Broughton KS Whelan JW : Dietary unsaturated fatty acids: Interactions and possible needs in relation to eicosanoid synthesis . J Nutr Biochem 1:123-141. 1990

11.

Meager A. Leung H. , Woolley J. : Assays for Tumor Necrosis Factor and Related Cytokines. J Immunol Methods 116:1-17, 1989

12.

Foegh ML : Eicosanoids and platelet activating factor mechanisms in organ rejection . Transplant Proc 20:1260-1263, 1988

13.

Goodwin JS , Webb DR : Regulation of the immune response by prostaglandins. Clin Immunol Immunopathol 15:106-111, 1980

14.

Kunkel SL , Chensue SW , Phan SH : Prostaglandins as endogenous mediators of interleukin 1 production . J Immunol 136:186-192, 1986

15.

Knudsen PJ , Dinarello CA , Strom TB : Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate . J Immunol 137:3189-3994, 1986

16.

Chouaib S. , Chatenoud L. , Klatzmann D. , et al: The mechanisms of inhibition of human IL-2 production. II. PG E2 induction of suppressor T-lymphocytes. J Immunol 132:1851-1857, 1984

17.

Budowski P. , Crawford MA : α - Linoleic acid as a regulator of the metabolism of arachidonic acid: n-6:n-3 fatty acids. Proc Nutr Soc 44:221, 1985

18.

Mead JF : The metabolism of the polyunsaturated fatty acids. IN Progress in The Chemistry of Fats and Other Lipids, Holman RT (ed). Pergamon Press, Elmsford , New York, 1968, pp 182-192

19.

Endres S. , Ghorbani R. , Kelley V. , 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. New Engl J Med 320:265-271, 1989