- Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, China;
Objective To investigate the immunoregulatory effects of immunonutrient ω-3 polyunsaturated fatty acid (PUFA) and its applications in organ transplantation.
Methods Relevant literatures of recent years were reviewed.
Results The immunoregulatory effects of ω-3 PUFA can inhibit proliferation and activation of the immunocompetent cells including T cell and B cell, reduce cytokine production, modulate immunologic response, improve graft function, pro-long survival, reduce episodes of rejection, and lessen adverse reactions of immunosuppressor.
Conclusion ω-3 PUFA should have wide applications in organ transplantation due to its immunoregulatory effects. However, this research should be further studied.
Citation： ZHANG Ming,LI Bo. Immunoregulatory Effects of ω-3 Polyunsaturated Fatty Acid and Its Applications in Organ Transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(4): 497-501. doi: Copy
| 1. | Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases [J]. J Am Coll Nutr, 2002； 21(6)∶495. |
| 2. | Bennett WM, Carpenter CB, Shapiro ME, et al. Delayed omega-3 fatty acid supplements in renal transplantation. A double-blind, placebo-controlled study[J].Transplantation， 1995； 59(3)∶352. |
| 3. | Maachi K, Berthoux P, Burgard G, et al. Results of a 1-year randomized controlled trial with omega-3 fatty acid fish oil in renal transplantation under triple immunosuppressive therapy [J]. Transplant Proc, 1995； 27(1)∶846. |
| 4. | Calder PC. Can n-3 polyunsaturated fatty acids be used as immunomodulatory agents? [J]. Biochem Soc Trans, 1996； 24(1)∶211 . |
| 5. | Vandenbroecke C, Caillat-Zucman S, Legendre C, et al. Differential in situ expression of cytokines in renal allograft rejection[J].Transplantation, 1991； 51(3)∶602. |
| 6. | Calder PC. Effects of fatty acids and dietary lipida on cells of the immune system[J]. Proc Nutr Soc, 1996； 55(1B)∶127. |
| 7. | Watson J, Madhok R, Wijelath E,et al. Mechanism of action of polyunsaturated fatty acids in rheumatoid arthritis [J]. Biochem Soc Trans, 1990； 18(2)∶284. |
| 8. | Furst P, Kuhn KS. Fish oil emulsions: what benefits can they bring?[J]. Clin Nutr， 2000; 19(1)∶7. |
| 9. | Yaqoob P, Newsholme E, Calder PC. The effect of dietary lipid manipulation on rat lymphocyte subsets and proliferation[J]. Immunology, 1994； 82(4)∶603. |
| 10. | Thies F, Nebe-von-caron G, Powell JR, et al. Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y [J]. Am J Clin Nutr, 2001； 73(4)∶539. |
| 11. | Mayer K, Fegbeutel C, Hattar K, et al. Omega-3 vs. omega-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation [J]. Intensive Care Med， 2003; 29(9)∶1472. |
| 12. | Thies F, Nebe-von-Caron G, Powell JR, et al. Dietary supplementation with gamma-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans [J]. J Nutr， 2001; 131(7)∶1918. |
| 13. | Weiss G, Meyer F, Matthies B, et al. Immunomodulation by perioperative administration of n-3 fatty acids [J]. Br J Nutr， 2002; 87 Suppl 1∶S89. |
| 14. | Ait-Said F, Elalamy I, Werts C, et al. Inhibition by eicosapentaenoic acid of IL-1beta-induced PGHS-2 expression in human microvascular endothelial cells: involvement of lipoxygenase-derived metabolites and p38 MAPK pathway [J]. Biochim Biophys Acta， 2003; 1631(1)∶77. |
| 15. | Dallman MJ, Roake J, Hughes D, et al. Sequential analysis of IL-2 gene transcription in renal transplants [J]. Transplantation, 1992； 53(3)∶683. |
| 16. | Mayer K, Gokorsch S, Fegbeutel C, et al. Parenteral nutrition with fish oil modulates cytokine response in patients with sepsis [J]. Am J Respir Crit Care Med， 2003; 167(10):1321. |
| 17. | Mayer K, Meyer S, Reinholz-Muhly M, et al. Short-time infusion of fish oil-based lipid emulsions, approved for parenteral nutrition, reduces monocyte proinflammatory cytokine generation and adhesive interaction with endothelium in humans [J]. J Immunol， 2003; 171(9)∶4837. |
| 18. | Schauder P, Rohn U, Schafer G, et al. Impact of fish oil enriched total parenteral nutrition on DNA synthesis, cytokine release and receptor expression by lymphocytes in the postoperative period [J]. Br J Nutr， 2002; 87 Suppl 1∶S103. |
| 19. | Alexander JW. Immunonutrition: the role of omega-3 fatty ac-ids[J]. Nutrition, 1998； 14(7-8)∶627. |
| 20. | Potois L, Deckelbaum RJ, Malaisse WJ, et al. Rapid accumulation of EPA in cellular phospholipids after iv injection of a fish oil and MCT containing lipid emulsion in normal subjects [J]. Clin Nutr Metab, 2004; 18(Supple)∶s53. |
| 21. | 王璇琳. 共轭亚油酸的免疫调节研究进展[J].国外医学免疫学分册， 2003； 26（4）∶204. |
| 22. | Philpott DJ, Yamaoka S, Israel A,et al. Invasive Shigella flexneri activates NF-kappa B through a lipopolysaccharide-dependent innate intracellular response and leads to IL-8 expression in epithelial cells[J].J Immunol, 2000； 165(2)∶903. |
| 23. | Zhu W, Downey JS, Gu J, et al. Regulation of TNF expression by multiple mitogen-activated protein kinase pathways[J]. J Immunol， 2000； 164(12)∶6349. |
| 24. | Lo CJ, Chiu KC, Fu M, et al. Fish oil modulates macrophage P44/P42 mitogen-activated protein kinase activity induced by lipopolysaccharide[J]. JPEN J Parenter Enteral Nutr, 2000; 24(3)∶159. |
| 25. | Novak TE, Babcock TA, Jho DH, et al. NF-kappa B inhibition by omega-3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription[J]. Am J Physiol Lung Cell Mol Physiol, 2003; 284(1)∶L84. |
| 26. | 刘秉文， 陈俊杰主编. 医学分子生物学 [J]. 第2版. 北京： 中国协和医科大学出版社， 2005∶137~160. |
| 27. | Gibson SW, Valente JF, Alexander JW, et al. The effect of nutritional immunomodulation on cardiac allograft survival in rats receiving mycophenolate mofetil, cyclosporine A, and donor-specific transfusion[J]. J Heart Lung Transplant, 1999； 18(3)∶185. |
| 28. | Grimm H, Tibell A, Norrlind B, et al. Nutrition and allorejection impact of lipids[J]. Transpl Immunol, 1995； 3(1)∶62. |
| 29. | Otto DA, Kahn DR, Hamm MW,et al. Improved survival of heterotopic cardiac allografts in rats with dietary n-3 polyunsaturated fatty acids[J]. Transplantation, 1990； 50(2)∶193. |
| 30. | Grimm H, Tibell A, Norrlind B, et al. Immunosuppression by n-3 fatty acids comparision of glycerol vs. ethyl esters[J]. Nutrition Research, 1996； 16(6)∶999. |
| 31. | Levy AE, Alexander JW. Nutritional immunomodulation enhances cardiac allograft survival in rats treated with donor-specific transfusion and cyclosporine [J].Transplantation,1995； 60(8)∶812. |
| 32. | Alexander JW, Levy A, Custer DA, et al. Arginine, fish oil, and donor-specific transfusions independently improve cardiac allograft survival in rats given subtherapeutic doses of cyclosporin [J]. JPEN J Parenter Enteral Nutr, 1998； 22(3)∶152. |
| 33. | Haw MP, Linnebjerg H, Chavali SR, et al. The effect of dietary polyunsaturated fatty acids (PUFA) on acute rejection and cardiac allograft blood flow in rats[J]. Transplantation, 1995; 60(6)∶570. |
| 34. | Homan van der Heide JJ, Bilo HJ, Tegzess AM, et al. The effects of dietary supplementation with fish oil on renal function in cyclosporine-treated renal transplant recipients [J].Transplantation， 1990； 49(3)∶523. |
| 35. | Homan van der Heide JJ, Bilo HJ, Donker AJ， et al. The effects of dietary supplementation with fish oil on renal function and the course of early postoperative rejection episodes in cyclosporine-treated renal transplant recipients [J].Transplantation, 1992； 54(2)∶257. |
| 36. | Homan van der Heide JJ, Bilo HJ, Donker AJ, et al. Effect of dietary fish oil on renal function and rejection in cyclosporine-treated recipients of renal transplants[J].N Engl J Med, 1993； 329(4)∶769. |
| 37. | Castro R, Queiros J, Fonseca I, et al. Therapy of post-renal tr-ansplantation hyperlipidaemia: comparative study with simvastatin and fish oil [J]. Nephrol Dial Transplant, 1997； 12(10)∶2140. |
| 38. | Domingo H, Roberto G, Antonio M, et al. Dietary fish oil does not influence acute rejection rate and graft survival after renal transplantation:a randomized placebo-controlled study[J]. Nephrol Dial Transplant, 2002； 17(6)∶897. |
| 39. | Ingale AV, Ingale FA, Kadam N, et al. Parenteral fish oil is safe in renal failure [J]. Clin Nutr, 2004; 23(4)∶69. |
| 40. | Badalamenti S, Salerno F, Lorenzano E, et al. Renal effects of dietary supplementation with fish oil in cyclosporine-treated liver transplant recipients[J]. Hepatology, 1995； 22(6)∶1695. |
| 41. | El-Badry AM, Moritz W, Contaldo C, et al. Prevention of reperfusion injury and microcirculatory failure in macrosteatotic mouse liver by omega-3 fatty acids[J]. Hepatology， 2007; 45(4)∶855. |
| 42. | Heller AR, Rossel T, Gottschlich B, et al. Omega-3 fatty acids improve liver and pancreas function in postoperative cancer patients[J]. Int J Cancer， 2004; 111(4)∶611. |
| 43. | Ventura HO, Milani RV, Lavie CJ, et al. Cyclosporine-indu-ced hypertension. Efficacy of omega-3 fatty acids in patients after cardiac transplantation [J]. Circulation, 1993; 88(5 Pt 2)∶Ⅱ281 . |
| 44. | Holm T, Andreassen AK, Aukrust P, et al. Omega-3 fatty acids improve blood pressure control and preserve renal function in hypertensive heart transplant recipients[J].Eur Heart J,2001; 22(5)∶428. |
- 1. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases [J]. J Am Coll Nutr, 2002； 21(6)∶495.
- 2. Bennett WM, Carpenter CB, Shapiro ME, et al. Delayed omega-3 fatty acid supplements in renal transplantation. A double-blind, placebo-controlled study[J].Transplantation， 1995； 59(3)∶352.
- 3. Maachi K, Berthoux P, Burgard G, et al. Results of a 1-year randomized controlled trial with omega-3 fatty acid fish oil in renal transplantation under triple immunosuppressive therapy [J]. Transplant Proc, 1995； 27(1)∶846.
- 4. Calder PC. Can n-3 polyunsaturated fatty acids be used as immunomodulatory agents? [J]. Biochem Soc Trans, 1996； 24(1)∶211 .
- 5. Vandenbroecke C, Caillat-Zucman S, Legendre C, et al. Differential in situ expression of cytokines in renal allograft rejection[J].Transplantation, 1991； 51(3)∶602.
- 6. Calder PC. Effects of fatty acids and dietary lipida on cells of the immune system[J]. Proc Nutr Soc, 1996； 55(1B)∶127.
- 7. Watson J, Madhok R, Wijelath E,et al. Mechanism of action of polyunsaturated fatty acids in rheumatoid arthritis [J]. Biochem Soc Trans, 1990； 18(2)∶284.
- 8. Furst P, Kuhn KS. Fish oil emulsions: what benefits can they bring?[J]. Clin Nutr， 2000; 19(1)∶7.
- 9. Yaqoob P, Newsholme E, Calder PC. The effect of dietary lipid manipulation on rat lymphocyte subsets and proliferation[J]. Immunology, 1994； 82(4)∶603.
- 10. Thies F, Nebe-von-caron G, Powell JR, et al. Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y [J]. Am J Clin Nutr, 2001； 73(4)∶539.
- 11. Mayer K, Fegbeutel C, Hattar K, et al. Omega-3 vs. omega-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation [J]. Intensive Care Med， 2003; 29(9)∶1472.
- 12. Thies F, Nebe-von-Caron G, Powell JR, et al. Dietary supplementation with gamma-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans [J]. J Nutr， 2001; 131(7)∶1918.
- 13. Weiss G, Meyer F, Matthies B, et al. Immunomodulation by perioperative administration of n-3 fatty acids [J]. Br J Nutr， 2002; 87 Suppl 1∶S89.
- 14. Ait-Said F, Elalamy I, Werts C, et al. Inhibition by eicosapentaenoic acid of IL-1beta-induced PGHS-2 expression in human microvascular endothelial cells: involvement of lipoxygenase-derived metabolites and p38 MAPK pathway [J]. Biochim Biophys Acta， 2003; 1631(1)∶77.
- 15. Dallman MJ, Roake J, Hughes D, et al. Sequential analysis of IL-2 gene transcription in renal transplants [J]. Transplantation, 1992； 53(3)∶683.
- 16. Mayer K, Gokorsch S, Fegbeutel C, et al. Parenteral nutrition with fish oil modulates cytokine response in patients with sepsis [J]. Am J Respir Crit Care Med， 2003; 167(10):1321.
- 17. Mayer K, Meyer S, Reinholz-Muhly M, et al. Short-time infusion of fish oil-based lipid emulsions, approved for parenteral nutrition, reduces monocyte proinflammatory cytokine generation and adhesive interaction with endothelium in humans [J]. J Immunol， 2003; 171(9)∶4837.
- 18. Schauder P, Rohn U, Schafer G, et al. Impact of fish oil enriched total parenteral nutrition on DNA synthesis, cytokine release and receptor expression by lymphocytes in the postoperative period [J]. Br J Nutr， 2002; 87 Suppl 1∶S103.
- 19. Alexander JW. Immunonutrition: the role of omega-3 fatty ac-ids[J]. Nutrition, 1998； 14(7-8)∶627.
- 20. Potois L, Deckelbaum RJ, Malaisse WJ, et al. Rapid accumulation of EPA in cellular phospholipids after iv injection of a fish oil and MCT containing lipid emulsion in normal subjects [J]. Clin Nutr Metab, 2004; 18(Supple)∶s53.
- 21. 王璇琳. 共轭亚油酸的免疫调节研究进展[J].国外医学免疫学分册， 2003； 26（4）∶204.
- 22. Philpott DJ, Yamaoka S, Israel A,et al. Invasive Shigella flexneri activates NF-kappa B through a lipopolysaccharide-dependent innate intracellular response and leads to IL-8 expression in epithelial cells[J].J Immunol, 2000； 165(2)∶903.
- 23. Zhu W, Downey JS, Gu J, et al. Regulation of TNF expression by multiple mitogen-activated protein kinase pathways[J]. J Immunol， 2000； 164(12)∶6349.
- 24. Lo CJ, Chiu KC, Fu M, et al. Fish oil modulates macrophage P44/P42 mitogen-activated protein kinase activity induced by lipopolysaccharide[J]. JPEN J Parenter Enteral Nutr, 2000; 24(3)∶159.
- 25. Novak TE, Babcock TA, Jho DH, et al. NF-kappa B inhibition by omega-3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription[J]. Am J Physiol Lung Cell Mol Physiol, 2003; 284(1)∶L84.
- 26. 刘秉文， 陈俊杰主编. 医学分子生物学 [J]. 第2版. 北京： 中国协和医科大学出版社， 2005∶137~160.
- 27. Gibson SW, Valente JF, Alexander JW, et al. The effect of nutritional immunomodulation on cardiac allograft survival in rats receiving mycophenolate mofetil, cyclosporine A, and donor-specific transfusion[J]. J Heart Lung Transplant, 1999； 18(3)∶185.
- 28. Grimm H, Tibell A, Norrlind B, et al. Nutrition and allorejection impact of lipids[J]. Transpl Immunol, 1995； 3(1)∶62.
- 29. Otto DA, Kahn DR, Hamm MW,et al. Improved survival of heterotopic cardiac allografts in rats with dietary n-3 polyunsaturated fatty acids[J]. Transplantation, 1990； 50(2)∶193.
- 30. Grimm H, Tibell A, Norrlind B, et al. Immunosuppression by n-3 fatty acids comparision of glycerol vs. ethyl esters[J]. Nutrition Research, 1996； 16(6)∶999.
- 31. Levy AE, Alexander JW. Nutritional immunomodulation enhances cardiac allograft survival in rats treated with donor-specific transfusion and cyclosporine [J].Transplantation,1995； 60(8)∶812.
- 32. Alexander JW, Levy A, Custer DA, et al. Arginine, fish oil, and donor-specific transfusions independently improve cardiac allograft survival in rats given subtherapeutic doses of cyclosporin [J]. JPEN J Parenter Enteral Nutr, 1998； 22(3)∶152.
- 33. Haw MP, Linnebjerg H, Chavali SR, et al. The effect of dietary polyunsaturated fatty acids (PUFA) on acute rejection and cardiac allograft blood flow in rats[J]. Transplantation, 1995; 60(6)∶570.
- 34. Homan van der Heide JJ, Bilo HJ, Tegzess AM, et al. The effects of dietary supplementation with fish oil on renal function in cyclosporine-treated renal transplant recipients [J].Transplantation， 1990； 49(3)∶523.
- 35. Homan van der Heide JJ, Bilo HJ, Donker AJ， et al. The effects of dietary supplementation with fish oil on renal function and the course of early postoperative rejection episodes in cyclosporine-treated renal transplant recipients [J].Transplantation, 1992； 54(2)∶257.
- 36. Homan van der Heide JJ, Bilo HJ, Donker AJ, et al. Effect of dietary fish oil on renal function and rejection in cyclosporine-treated recipients of renal transplants[J].N Engl J Med, 1993； 329(4)∶769.
- 37. Castro R, Queiros J, Fonseca I, et al. Therapy of post-renal tr-ansplantation hyperlipidaemia: comparative study with simvastatin and fish oil [J]. Nephrol Dial Transplant, 1997； 12(10)∶2140.
- 38. Domingo H, Roberto G, Antonio M, et al. Dietary fish oil does not influence acute rejection rate and graft survival after renal transplantation:a randomized placebo-controlled study[J]. Nephrol Dial Transplant, 2002； 17(6)∶897.
- 39. Ingale AV, Ingale FA, Kadam N, et al. Parenteral fish oil is safe in renal failure [J]. Clin Nutr, 2004; 23(4)∶69.
- 40. Badalamenti S, Salerno F, Lorenzano E, et al. Renal effects of dietary supplementation with fish oil in cyclosporine-treated liver transplant recipients[J]. Hepatology, 1995； 22(6)∶1695.
- 41. El-Badry AM, Moritz W, Contaldo C, et al. Prevention of reperfusion injury and microcirculatory failure in macrosteatotic mouse liver by omega-3 fatty acids[J]. Hepatology， 2007; 45(4)∶855.
- 42. Heller AR, Rossel T, Gottschlich B, et al. Omega-3 fatty acids improve liver and pancreas function in postoperative cancer patients[J]. Int J Cancer， 2004; 111(4)∶611.
- 43. Ventura HO, Milani RV, Lavie CJ, et al. Cyclosporine-indu-ced hypertension. Efficacy of omega-3 fatty acids in patients after cardiac transplantation [J]. Circulation, 1993; 88(5 Pt 2)∶Ⅱ281 .
- 44. Holm T, Andreassen AK, Aukrust P, et al. Omega-3 fatty acids improve blood pressure control and preserve renal function in hypertensive heart transplant recipients[J].Eur Heart J,2001; 22(5)∶428.