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Nutritional modulation of immune function

Published online by Cambridge University Press:  05 March 2007

R. F. Grimble*
Institute of Human Nutrition, School of Medicine, University of Southampton, Southampton SO16 7PX, UK
Corresponding Author: Professor Bob Grimble, fax +44 23 8059 7302, email
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The inflammatory response to injury and infection, although an essential part of immune function, carries the risk of severe tissue depletion and immunosuppression. These outcomes increase morbidity and delay recovery. Evidence is accumulating that single-nucleotide polymorphisms in the genes controlling pro-inflammatory cytokine production adversely influence the response. Immunonutrition provides a means of modulating the inflammatory response to injury and infection, and thereby improves clinical outcome. n-3 Polyunsaturated fatty acids (n-3 PUFA), glutamine, arginine, S amino acids and nucleotides are important components of immunonutrient mixes. While animal model studies suggest that all these components may exert a beneficial effect in patients, the number of large randomized placebo-controlled trials utilizing immunonutrition is fairly limited and the observed effects are relatively small. Meta-analyses suggest that while immunonutrition may not reduce mortality rates, a reduction in hospital length of stay, decreased requirements for ventilation and lower infection rates are achieved by this mode of nutrition. The present paper discusses some underlying reasons for the difficulty in demonstrating the clinical efficacy of immunonutrition. Paramount among these reasons is the antioxidant status and genetic background of the patient. A number of studies suggest that there is an inverse relationship between inflammation and T-cell function. Immuno-enhancive effects have been shown in a number of studies in which n-3 PUFA, glutamine and N-acetyl cysteine have been employed. All these nutrients may exert their effects by suppressing inflammation; n-3 PUFA by direct suppression of the process and glutamine and N-acetyl cysteine by acting indirectly on antioxidant status. Glutamine and nucleotides exert a direct effect on lymphocyte proliferation. Preliminary data suggests that not all genotypes are equally sensitive to the effects of immunonutrition. When further studies have been conducted to discern the precise interaction between each individual's genotype of relevance to the response to injury and infection, and immunonutrients, the level of precision in the application of immunonutrition will undoubtedly improve.

Symposium on ‘Evidence-based nutrition’
Copyright © The Nutrition Society 2001


Arnalich, F, Garcia-Palomero, E, Lopez, J, Jiminez, M, Madero, R, Renart, J, Vazquez, JJ & Montiel, C (2000) Predictive value of nuclear factor kappaB activity and plasma cytokine levels in patients with sepsis. Infection and Immunity 68, 19421945.Google Scholar
Asano, H, Kobayashi, T, Uchida, K, Hayashi, S, Yokoyama, I, Inoko, H & Takagi, H (1997) Significance of tumor necrosis factor microsatellite polymorphism in renal transplantation. Tissue Antigens 50, 484488.Google Scholar
Beale, RJ, Bryg, DJ & Bihari, DJ (1999) Immunonutrition in the critically ill: A systematic review of clinical outcome. Critical Care Medicine 27, 27992805.Google Scholar
Boya, P, de la Pena, A, Beloqui, O, Larrea, E, Conchillo, M, Castelruiz, Y, Civeira, MP & Prieto, J (1999) Antioxidant status and glutathione metabolism in peripheral blood mononuclear cells from patients with chronic hepatitis C. Journal of Hepatology 31, 808814.Google Scholar
Braga, M, Gionotti, L, Radaelli, G, Vignoli, A, Mori, G, Gentilini, O & di Carlo, V (1999) Perioperative immunonutrition in patients undergoing cancer surgery. Results of a randomized double-blind phase 3 trial. Archives of Surgery 134, 428433.Google Scholar
Breitkreutz, R, Pittack, N, Nebe, CT, Schuster, D, Brust, J, Beichert, M, Hack, V, Daniel, V, Edler, L & Droge, W (2000) Improvement of immune functions in HIV infection by sulfur supplementation: Two randomized trials. Journal of Molecular Medicine 78, 5562.Google Scholar
Calder, PC (1997) n-3 Polyunsaturated fatty acids and cytokine production in health and disease. Annals of Nutrition and Metabolism 41, 203234.Google Scholar
Cao, Y, Feng, Z, Hoos, A & Klimberg, VS (1998) Glutamine enhances gut glutathione production. Journal of Parenteral and Enteral Nutrition 22, 224227.Google Scholar
Choi, SS, Gatanaga, M, Granger, GA & Gatanaga, T (1996) Prostaglandin-E2 regulation of tumor necrosis factor receptor release in human monocytic THP-1 cells. Cellular Immunology 170, 178184.Google Scholar
Cowley, HC, Bacon, PJ, Goode, HF, Webster, NR, Jones, JG & Menon, DK (1996) Plasma antioxidant potential in severe sepsis: A comparison of survivors and nonsurvivors. Critical Care Medicine 24, 11791183.Google Scholar
Denno, R, Rounds, JD, Faris, R, Halejko, LB & Wilmore, DW (1996) Glutamine enriched TPN enhances plasma glutathione in resting state. Journal of Surgical Research 61, 3538.Google Scholar
Dröge, W, Schulze-Osthoff, K, Mihm, S, Galter, D, Schenk, H, Eck, HP, Roth, S & Gmünder, H (1994) Functions of glutathione and glutathione disulphide in immunology and immunopathology. FASEB Journal 8, 11311138.Google Scholar
Elia, M (1992) Glutamine in parenteral nutrition. International Journal of Food Science and Nutrition 43, 4749.Google Scholar
Endres, S, Ghorbani, R, Kelley, VE, Georgilis, K, Lonnemann, G, van der Meer, JWM, Cannon, JG, Rogers, TS, Klempner, MS, Weber, PC, Schaefer, EJ, Wolff, SM & Dinarello, CA (1989) 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 England Journal of Medicine 320, 265271.Google Scholar
Gadek, JE, De Michele, SJ, Karlstad, MD, Pocht, ER, Donahoe, M, Albertson, TE, Van Hoozen, C, Wennberg, AK, Nelson, JL, Nourselehi, M and the Enteral Nutrition in ARDS Study Group (1999) Effect of enteral feeding with eicosapentaenoic acid, g-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Critical Care Medicine 27, 14091420.Google Scholar
Gerster, H (1995) The use of n-3 PUFAs (fish oil) in enteral nutrition. International Journal of Vitamin and Nutrition Research 65, 320.Google Scholar
Gionotti, L, Braga, M, Fortis, C, Soldini, L, Vignoli, A, Colombo, S, Radaelli, G & di Carlo, V (1999) A prospective randomized clinical trial on perioperative feeding with arginine, omega 3 fatty acid, and RNA-enriched enteral diet. Effect on host response and nutrient status. Journal of Parenteral and Enteral Nutrition 23, 314320.Google Scholar
Grimble, RF (1998a) Nutritional modulation of cytokine biology. Nutrition 14, 634640.Google Scholar
Grimble, RF (1998b) Dietary lipids and the inflammatory response. Proceedings of the Nutrition Society 57, 535542.Google Scholar
Grimble, RF, Calder, PC, Howell, WM, O'Reilly, GM, Turner, S, Markovic, O & East, JM (2001) The ability of fish oil to suppress TNF-α production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes which influence TNF-α production. American Journal of Clinical Nutrition (In the Press).Google Scholar
Hohler, T, Kruger, A, Gerken, G, Schneider, PM, Meyer zum Buschenefelde, KH & Rittner, C (1998) A tumor necrosis factor-alpha (TNF-alpha) promoter polymorphism is associated with chronic hepatitis C infection. Journal of Medical Virology 54, 173177.Google Scholar
Houdijk, APJ, Rijnsburger, ER, Jansen, J, Wesdorp, RIC, Weiss, JK, McCamish, MA, Teerlink, T, Meuwissen, SGM, Haarman, HJThM, Thijs, LG & Van Leeuwen, PAM (1998) Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 352, 772776.Google Scholar
Hutchinson, IV, Pravica, V, Hajeer, A & Sinnott, PJ (1999) Identification of high and low responders to allographs. Review in Immunogenetics 1, 323333.Google Scholar
Jackson, MJ, McArdle, A & McArdle, F (1998) Antioxidant micronutrients and gene expression. Proceedings of the Nutrition Society 57, 301305.Google Scholar
Jacob, CO, Franek, Z, Lewis, GD, Koo, M, Hansen, JA & McDevitt, HO (1990) Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor-a: Relevance to genetic predisposition to systemic lupus erythematosus. Proceedings of the National Academy of Sciences USA 87, 12331237.Google Scholar
Kelley, DS, Taylor, PC, Nelson, GJ, Schmidt, PC, Ferretti, A, Erickson, KL, Yu, R, Chandra, RK & Mackay, BE (1999) Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in healthy men. Lipids 34, 317324.Google Scholar
Loguercio, C, Blanco, FD, De Girolamo, V, Disalvo, D, Nardi, G, Parente, A & Blanco, CD (1999) Ethanol consumption, amino acid and glutathione blood levels in patients with and without chronic liver disease. Alcohol Clinical and Experimental Research 23, 17801784.Google Scholar
Luo, JL, Hammarqvist, F, Andersson, K & Wernerman, J (1996) Skeletal muscle glutathione after surgical trauma. Annals of Surgery 223, 420427.Google Scholar
McGuire, W, Hill, AV, Allsopp, CE, Greenwood, BM & Kwaitkowski, D (1994) Variations in the TNF-α promoter region associated with susceptibility to cerebral malaria. Nature 371, 508511.Google Scholar
McWhirter, JP & Pennington, CR (1994) Incidence and recognition of malnutrition in hospital. British Medical Journal 308, 945948.Google Scholar
Majetschak, M, Flohe, S, Obertacke, V, Schroder, J, Staubach, K, Nast-Kolb, D, Schade, V & Stuber, F (1999) Relationships of a TNF gene polymorphism to severe sepsis in trauma patients. Annals of Surgery 230, 207214.Google Scholar
Meydani, SN, Meydani, M, Blumberg, JB, Leka, LS, Silber, G, Loszewski, R, Thompson, C, Pedrosa, MC, Diamond, RD & Stoller, D (1997) Vitamin E supplementation and in vivo immune response in healthy subjects. A randomized controlled trial. Journal of the American Medical Association 277, 13701386.Google Scholar
Micke, P, Beeh, KM, Schlaak, JF & Buhl, R (2001) Oral supplementation with whey proteins increases plasma glutathione levels in HIV-infected patients. European Journal of Clinical Investigation 31, 171178.Google Scholar
Mol, JTM, de Rijke, YB, Demacher, PNM & Stalenhoef, AFH (1997) Plasma levels of lipid and cholesterol oxidation products and cytokines in diabetes mellitus and smokers: effect of vitamin E treatment. Atherosclerosis 129, 169176.Google Scholar
Morlion, BJ, Stehle, P, Wachtler, P, Siedhoff, H-P, Koller, M, Konig, W, Furst, P & Puchstein, C (1998) Total parenteral nutrition with glutamine dipeptide after major surgery. A double blind controlled study. Annals of Surgery 227, 302308.Google Scholar
Newsholme, EA, Crabtree, B, Salleh, M & Ardawi, M (1985) Glutamine metabolism in lymphocytes. Its biochemistry, physiology and clinical importance. Quarterly Journal of Experimental Physiology 70, 473489.Google Scholar
Nuttall, SL, Dunne, F, Kendall, MJ & Martin, U (1999) Age-dependent oxidative stress in elderly patients with non-insulin-dependent diabetes mellitus. Quarterly Journal of Medicine 92, 3338.Google Scholar
O'Flaherty, L & Bouchier-Hayes, DJ (1999) Immunonutrition and surgical practice. Proceedings of the Nutrition Society 58, 831837.Google Scholar
Pociot, F, Briant, L & Jongeneel, CV (1993) Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-α and TNF-β by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. European Journal of Immunology 23, 224231.Google Scholar
Reid, M, Badaloo, A, Forrester, T, Morlese, JF, Frazer, M, Heird, WC & Jahoor, F (2000) In vivo rates of erythrocyte glutathione synthesis in children with severe protein-energy malnutrition. American Journal of Physiology 278, E405E412.Google Scholar
Ross, R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362, 801809.Google Scholar
Spapen, H, Zhang, H, Demanet, C, Vleminckx, W, Vincent, JL & Huyghens, L (1998) Does N-acetyl cysteine influence cytokine response during early human septic shock? Chest 113, 16161624.Google Scholar
Stüber, F, Petersen, M & Bokelmann, FA (1996) Genomic polymorphisms within the tumor necrosis factor locus influences plasma TNF-α concentrations and outcome of patients with sepsis. Critical Care Medicine 24, 381384.Google Scholar
Turner, D, Grant, SC, Yonan, N, Sheldon, S, Dyer, PA, Sinnott, PJ & Hutchinson, IV (1997) Cytokine gene polymorphism and heart transplant rejection. Transplantation 64, 776779.Google Scholar
Wu, D, Meydani, SN, Sastre, J, Hayek, M & Meydani, M (1994) In vitro glutathione supplementation enhances interleukin-2 production and mitogenic responses in peripheral blood mononuclear cells from young and old subjects. Journal of Nutrition 124, 655663.Google Scholar
Yaqoob, P, Pala, HS, Cortina-Borja, M, Newsholme, EA & Calder, PC (2000) Encapsulated fish oil enriched in alpha-tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions. European Journal of Clinical Nutrition 30, 399410.Google Scholar