Hostname: page-component-797576ffbb-5676f Total loading time: 0 Render date: 2023-12-08T10:58:19.581Z Has data issue: false Feature Flags: { "corePageComponentGetUserInfoFromSharedSession": true, "coreDisableEcommerce": false, "useRatesEcommerce": true } hasContentIssue false

The scientific basis of immunonutrition

Published online by Cambridge University Press:  28 February 2007

U. Suchner*
Clinic of Anesthesiology, Grosshadern, Ludwig Maximilians University, Marchioninistrasse 15, 81377 Munich, Germany
K. S. Kuhn
Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstr. 30, 70593 Stuttgart, Germany
P. Fürst
Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstr. 30, 70593 Stuttgart, Germany
*Corresponding author:Dr U. Suchner, present address Fresenius Kabi Deutschland GmbH, Else-Kröner-Strasse 1, 61352 Bad Homburg v.d.H., Germany, fax +49 6172 686 5505, email
Rights & Permissions [Opens in a new window]


Core share and HTML view are not possible as this article does not have html content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Substrates with immune-modulating actions have been identified among both macro- and micronutrients. Currently, the modes of action of individual immune-modulating substrates, and their effects on clinical outcomes, are being examined. At present, some enteral formulas are available for the clinical setting which are enriched with selected immune-modulating nutrients. The purpose of the present paper is to review the scientific rationale of enteral immunonutrition. The major aspects considered are mucosal barrier structure and function, cellular defence function and local or systemic inflammatory response. It is notable that in critical illness the mucosal barrier and cellular defence are impaired and a reinforcement with enteral immunonutrition is desirable, while local or systemic inflammatory response should be down regulated by nutritional interventions. The results available from clinical trials are conflicting. Meta-analyses of recent trials show improvements such as reduced risk of infection, fewer days on a ventilator, and reduced length of intensive care unit and hospital stay. Thus, a grade A recommendation was proclaimed for the clinical use of enteral immune-modulating diets. Improvement in outcome was only seen when critical amounts of the immune-modulating formula were tolerated in patients classified as being malnourished. However, in other patients with severe sepsis, shock and organ failure, no benefit or even disadvantages from immunonutrition were reported. In such severe conditions we hypothesize that systemic inflammation might be undesirably intensified by arginine and unsaturated fatty acids, directly affecting cellular defence and inflammatory response. We therefore recommend that in patients suffering from systemic inflammatory response syndrome great caution should be exercised when immune-enhancing substrates are involved which may aggravate systemic inflammation.

Clinical Nutrition and Metabolism Group Symposium on ‘Nutrition in the severely-injured patient’
Copyright © The Nutrition Society 2000


Albina, JE (1996) Nitric oxide regulation of inflammation and immunity. In Pharmacological Nutrition Immune Nutrition, pp. 2132 [Cynober, L, Fürst, P and Lawin, P, editors]. München: W. Zuckerschwerdt Verlag.Google Scholar
Alexander, JW, Saito, H, Trocki, O & Ogle, CK (1986) The importance of lipid type in the diet after burn. Annals of Surgery 204, 18.Google Scholar
Alverdy, JC (1990) Effects of glutamine-supplemented diets on immunology of the gut. Journal of Parenteral and Enteral Nutrition 14, 109S113S.Google Scholar
Atkinson, S, Sieffert, E & Bihari, D (1998) A prospective, randomized, double-blind, controlled clinical trial of enteral immunonutrition in the critically ill. Critical Care Medicine 26, 11641172.Google Scholar
Aw, TY (1997) Luminal peroxides in intestinal thiol-disulfide balance and cell turnover. Comparative Biochemistry and Physiology 118B, 479485.Google Scholar
Babst, R, Hörig, H, Stehle, P, Brand, O, Filgueira, L, Marti, W, Fischer, M, Oberholzer, M, Gudat, F, Fürst, P & Heberer, M (1993) Glutamine peptide-supplemented long-term total parenteral nutrition: effects on intracellular and extracellular amino acid patterns, nitrogen economy, and tissue morphology in growing rats. Journal of Parenteral and Enteral Nutrition 17, 566574.Google Scholar
Barbul, A (1986) Arginine: Biochemistry, physiology and therapeutic implications. Journal of Parenteral and Enteral Nutrition 10, 227238.Google Scholar
Barbul, A (1990) Arginine and immune function. Nutrition 6, 5358.Google Scholar
Barbul, A, Lazarou, SA, Efron, DT, Wasserkrug, HL & Efron, G (1990) Arginine enhances wound healing and lymphocyte response in humans. Surgery 108, 331337.Google Scholar
Barbul, A, Rettura, G, Levenson, SM & Seifter, E (1983) Wound healing and thymotropic effects of arginine: a pituitary mechanism of action. American Journal of Clinical Nutrition 37, 786794.Google Scholar
Barton, RG, Wells, CL, Carlson, A, Singh, R, Sullivan, JJ & Cerra, FC (1991) Dietary omega-3 fatty acids decrease mortality and Kupffer cell prostaglandin E2 production in a rat model of chronic sepsis. Journal of Trauma 31, 768774.Google Scholar
Bauer, P, Charpentier, C, Bouchet, C, Raffy, F, Gaconnet, N & Larcan, A (1998) Short parenteral nutrition coupled with early enteral nutrition in the critically ill. Intensive Care Medicine 24, S123.Google Scholar
Beale, JR, Bryg, DJ & Bihari, DJ (1999) Immunonutrition in the critically ill: A systematic review of clinical outcome. Critical Care Medicine 27, 27992805.Google Scholar
Beaumier, L, Castillo, L, Ajami, AM & Young, VR (1995) Urea cycle intermediate kinetics and nitrate excretion at normal and 'therapeutic' intakes of arginine in humans. American Journal of Physiology 269, E884E896.Google Scholar
Bergström, J, Fürst, P, Noree, L-O, & Vinnars, E (1974) Intracellular free amino acid concentration in human muscle tissue. Journal of Applied Physiology 36, 693697.Google Scholar
Blachier, F, Darcy-Vrillon, B, Sener, A, Duee, PH & Malaisse, WJ (1991) Arginine metabolism in rat enterocytes. Biochimica et Biophysica Acta 1092, 304310.Google Scholar
Bode, BP & Souba, WW (1994) Modulation of cellular proliferation alters glutamine transport and metabolism in human hepatoma cells. Annals of Surgery 220, 411424.Google Scholar
Bower, RH (1990) Nutrition and immune function. Nutrition in Clinical Practice 5, 189195.Google Scholar
Bower, RH, Cerra, FB, Bershadsky, B, Licari, JJ, Hoyt, DB, Jensen, GL, Van Buren, CT, Rothkopf, MM, Daly, JM & Adelsberg, BR (1995) Early enteral administration of a formula (Impact®) supplemented with arginine, nucleotides and fish oil in intensive care patients: Results of a multicenter, prospective, randomized clinical trial. Critical Care Medicine 23, 436449.Google Scholar
Braga, M, Gianotti, L, Vignali, A, Cestari, A, Bisagni, P & Di, CV (1998) Artificial nutrition after major abdominal surgery: impact of route of administration and composition of the diet. Critical Care Medicine 26, 2430.Google Scholar
Brittenden, J, Heys, SD, Ross, J, Park, KG & Eremin, O (1994 a) Nutritional pharmacology: effects of L-arginine on host defences, response to trauma and tumour growth. Clinical Science 86, 123132.Google Scholar
Brittenden, J, Park, KG, Heys, SD, Ross, C, Ashby, J, Ah-See, A & Eremin, O (1994 b) L-Arginine stimulates host defenses in patients with breast cancer. Surgery 115, 205212.Google Scholar
Burton, RG (1994) Nutrition support in critical illness. Nutrition in Clinical Practice 9, 127139.Google Scholar
Calder, PC (1994) Glutamine and the immune system. Clinical Nutrition 13, 28.Google Scholar
Calder, PC (1995) Fuel utilization by cells of the immune system. Proceedings of the Nutrition Society 54, 6582.Google Scholar
Calder, PC & Newsholme, EA (1992) Glutamine promotes interleukin-2 production by concanavalin A-stimulated lymphocytes. Proceedings of the Nutrition Society 51, 105A.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
Carver, JD, Cox, WI & Barness, LA (1990) Dietary nucleotide effects upon murine natural killer cell activity and macrophage activation. Journal of Parenteral and Enteral Nutrition 14, 1822.Google Scholar
Caughey, GE, Mantzioris, E, Gibson, RA, Cleland, LG & James, MJ (1996) The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. American Journal of Clinical Nutrition 63, 116122.Google Scholar
Cerra, FB (1991) Nutrient modulation of inflammatory and immune function. American Journal of Surgery 161, 230234.Google Scholar
Cerra, FB, Lehman, S, Konstantinides, N, Konstantinides, F, Shronts, EP & Holman, R (1990) Effect of enteral nutrient on in vitro tests of immune function in ICU patients: a preliminary report. Nutrition 6, 8487.Google Scholar
Chandra, RK (1991) Nutrition and immunity; lessons from the past and insights into the future. American Journal of Clinical Nutrition 52, 10871101.Google Scholar
Chow, A & Zhang, R (1998) Glutamine reduces heat shock-induced cell death in rat intestinal epithelial cells. Journal of Nutrition 128, 12961301.Google Scholar
Cosgrove, M (1998) Perinatal and infant nutrition. Nucleotides. Nutrition 14, 748751.Google Scholar
Daly, JM, Lieberman, MD, Goldfine, J, Shou, J, Weintraub, F, Rosato, EF & Lavin, P (1992) Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome. Surgery 112, 5667.Google Scholar
Daly, JM, Reynolds, J & Thom, A (1988) Immune and metabolic effects of arginine in the surgical patient. Annals of Surgery 208, 512523.Google Scholar
deGraaf, JC, Banga, JD, Moncada, S, Palmer, RM, de Groot, PG & Sixma, JJ (1992) Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions. Circulation 85, 22842290.Google Scholar
Denno, R, Rounds, JD, Faris, R, Holejko, LB & Wilmore, DW (1996) Glutamine-enriched total parenteral nutrition enhances plasma glutathione in the resting state. Journal of Surgical Research 61, 3538.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 IL-1 and TNF alpha by mononuclear cells. New England Journal of Medicine 320, 265271.Google Scholar
Endres, S, Meydani, SN & Dinarello, CA (1991) Effects of omega 3 fatty acid supplements on ex vivo synthesis of cytokines in human volunteers. Comparison with oral aspirin and ibuprofen. World Review of Nutrition and Dietetics 66, 401406.Google Scholar
Endres, S, Meydani, SN, Ghorbani, R, Schindler, R & Dinarello, CA (1993) Dietary supplementation with n-3 fatty acids suppresses interleukin-2 production and mononuclear cell proliferation. Journal of Leukocyte Biology 54, 599603.Google Scholar
Engstrom, K, Luostarinen, R & Saldeen, T (1996) Whole blood production of thromboxane, prostacyclin and leukotriene B4 after dietary fish oil supplementation in man: effect of vitamin E. Prostaglandins Leucotrienes and Essential Fatty Acids 54, 419425.Google Scholar
Ertel, W, Morrison, MH, Ayala, A & Chaudry, IH (1993) Modulation of macrophage membrane phospholipids by n-3 polyunsaturated fatty acids increases interleukin 1 release and prevents suppression of cellular immunity following hemorrhagic shock. Archives of Surgery 128, 1520.Google Scholar
Evoy, D, Lieberman, MD, Fahey, TJ III & Daly, JM (1998) Immunonutrition: The role of arginine. Nutrition 14, 611617.Google Scholar
Fanslow, WC, Kulkarni, AD, Van, BC & Rudolph, FB (1988) Effect of nucleotide restriction and supplementation on resistance to experimental murine candidiasis. Journal of Parenteral and Enteral Nutrition 12, 4952.Google Scholar
Fritsche, KL & Cassity, NA (1992) Dietary n-3 fatty acids reduce antibody-dependent cell cytotoxicity and alter eicosanoid release by chicken immune cells. Poultry Science 71, 16461657.Google Scholar
Furukawa, S, Saito, H, Inaba, T, Lin, MT, Inoue, T, Naka, S, Fukatsu, K, Hashiguchi, Y, Han, I, Matsuda, T, Ikeda, S & Muto, T (1997) Glutamine-enriched enteral diet enhances bacterial clearance in protected bacterial peritonitis, regardless of glutamine form. Journal of Parenteral and Enteral Nutrition 21, 208214.Google Scholar
Fürst, P (1994 a) New parenteral substrates in clinical nutrition. Part I Introduction. New substrates in protein nutrition. European Journal of Clinical Nutrition 48, 607616.Google Scholar
Fürst, P (1994 b) New parenteral substrates in clinical nutrition. Part II. New substrates in lipid nutrition. European Journal of Clinical Nutrition 48, 681691.Google Scholar
Fürst, P (1998) Old and new substrates in clinical nutrition. Journal of Nutrition 128, 789796.Google Scholar
Fürst, P & Kuhn, KS (2000) Fish oil emulsions – what benefits can they bring? Clinical Nutrition 19, 714.Google Scholar
Fürst, P & Stehle, P (1995) Parenteral nutrition substrates. In Artificial Nutrition Support in Clinical Practice, 1st ed., pp. 301322 [Payne-James, J, Grimble, G and Silk, D, editors]. London: Edward Arnold.Google Scholar
Gardiner, KR, Kirk, SJ & Rowlands, BJ (1995) Novel substrates to maintain gut integrity. Nutrition Research Reviews 8, 4366.Google Scholar
Gennari, R & Alexander, JW (1997) Arginine, glutamine, and dehydroepiandrosterone reverse the immunosuppressive effect of prednisone during gut-derived sepsis. Critical Care Medicine 25, 12071214.Google Scholar
Gonce, SJ, Peck, MD, Alexander, JW & Miskell, PW (1990) Arginine supplementation and its effect on established peritonitis in guinea pigs. Journal of Parenteral and Enteral Nutrition 14, 237244.Google Scholar
Griffiths, M & Keast, D (1990) The effect of glutamine on murine splenic leukocyte responses to T and B cell mitogens. Immunology and Cell Biology 68, 405408.Google Scholar
Griffiths, RD (1999) Glutamine: establishing clinical indications. Current Opinion in Clinical Nutrition and Metabolic Care 2, 177182.Google Scholar
Grimble, GK (1994) Essential and conditionally essential nutrients in clinical nutrition. In Organ Metabolism and Nutrition. Ideas for Future Critical Care. 1st ed., pp. 267299 [Kinney, JM and Tucker, HN, editors]. New York: Raven Press.Google Scholar
Grimble, RF (1992) Dietary manipulation of the inflammatory response. Proceedings of the Nutrition Society 51, 285294.Google Scholar
Grimble, RF (1998) Dietary lipids and the inflammatory response. Proceedings of the Nutrition Society 57, 535542.Google Scholar
Harbige, LS (1998) Dietary n-6 and n-3 fatty acids in immunity and autoimmune disease. Proceedings of the Nutrition Society 57, 555562.Google Scholar
Harward, TR, Coe, D, Souba, WW, Klingman, N & Seeger, JM (1994) Glutamine preserves gut glutathione levels during intestinal ischemia/reperfusion. Journal of Surgical Research 56, 351355.Google Scholar
Häussinger, D, Roth, E, Lang, F & Gerok, W (1993) Cellular hydration state: an important determinant of protein catabolism in health and disease. Lancet 341, 13301332.Google Scholar
Heyland, DK, Cook, DJ & Guyatt, GH (1994) Does the formulation of enteral feeding products influence infectious morbidity and mortality rates in critically ill patients? A critical review of the evidence. Critical Care Medicine 22, 11921202.Google Scholar
Heys, SD, Walker, LG, Smith, I & Eremin, O (1999) Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized, controlled clinical trials. Annals of Surgery 229, 467477.Google Scholar
Hong, RW, Rounds, JD, Helton, WS, Robinson, MK & Wilmore, DW (1992) Glutamine preserves liver glutathione after lethal hepatic injury. Annals of Surgery 215, 114119.Google Scholar
Horig, H, Spagnoli, GC, Filgueira, L, Babst, R, Gallati, H, Harder, F, Juretic, A & Heberer, M (1993) Exogenous glutamine requirement is confined to late events of T cell activation. Journal of Cell Biochemistry 53, 343351.Google Scholar
Houdijk, AP, Rijnsburger, ER, Jansen, J, Wesdorp, RI, Weiss, JK, McCamish, MA, Teerlink, T, Meuwissen, SG, Haarman, HJ, Thijs, LG & Van Leeuwen, PA (1998) Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 352, 772776.Google Scholar
Houdijk, AP, Teerlink, T, Bloemers, FW, Wesdorp, RI & Van Leeuwen, PA (1997) Gut endotoxin restriction prevents catabolic changes in glutamine metabolism after surgery in the bile duct-ligated rat. Annals of Surgery 225, 391400.Google Scholar
Houdijk, APJ (1998) Glutamine-enriched enteral nutrition in patients with multiple trauma. Lancet 352, 1553.Google Scholar
Iijima, S, Tsujinaka, T, Kido, Y, Hayashida, Y, Ishida, H, Homma, T, Yokoyama, H & Mori, T (1993) Intravenous administration of nucleosides and a nucleotide mixture diminishes intestinal mucosal atrophy induced by total parenteral nutrition. Journal of Parenteral and Enteral Nutrition 17, 265270.Google Scholar
Jones, C, Palmer, TE & Griffiths, RD (1999) Randomized clinical outcome study of critically ill patients given glutamine-supplemented enteral nutrition. Nutrition 15, 108115.Google Scholar
Juretic, A, Spagnoli, GC, Horig, H, Babst, R, Van Bremen, K, Harder, F & Heberer, M (1994) Tissue-specific gene expression results from a purine- and pyrimidine-free diet and 6-mercaptopurine in the rat small intestine and colon. Clinical Nutrition 13, 4249.Google Scholar
Jyonouchi, H (1994) Nucleotide actions on humoral immune responses. Journal of Nutrition 124, 138S143S.Google Scholar
Kelly, FJ (1993) Glutathione content of the small intestine: regulation and function. British Journal of Nutrition 69, 589596.Google Scholar
Kemen, M, Senkal, M, Homann, H-H, Mumme, A, Dauphin, A-K, Baier, M, Windeler, J, Neumann, H & Zumtobel, V (1995) Early postoperative enteral nutrition with arginine, n-3 fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients: An immunologic evaluation of Impact®. Critical Care Medicine 23, 652659.Google Scholar
Kinsella, JE, Lokesh, B, Broughton, S & Whelan, J (1990) Dietary polyunsaturated fatty acids and eicosanoids: potential effects on modulation of inflammatory and immune cells. An overview. Nutrition 6, 2444.Google Scholar
Kirk, SJ & Barbul, A (1990) Role of arginine in trauma, sepsis, and immunity. Journal of Parenteral and Enteral Nutrition 14, 226S229S.Google Scholar
Klimberg, VS, Souba, WW & Salloum, RM (1990) Intestinal glutamine metabolism after massive small bowel resection. American Journal of Surgery 159, 2733.Google Scholar
Kubes, P (1993) Ischemia-reperfusion in feline small intestine: a role for nitric oxide. American Journal of Physiology 264, G143G149.Google Scholar
Kudsk, KA, Minard, G, Croce, MA, Brown, RO, Lowrey, TS, Pritchard, E, Dickerson, RN & Fabian, TC (1996) A randomized trial of isonitrogeneous enteral diets after severe trauma. Annals of Surgery 224, 531543.Google Scholar
Kulkarni, A, Fanslow, W, Higley, H, Pizzini, R, Rudolph, F & Van, BC (1989) Expression of immune cell surface markers in vivo and immune competence in mice by dietary nucleotides. Transplantation Proceedings 21, 121124.Google Scholar
Kulkarni, AD, Fanslow, WC, Drath, DB, Rudolph, FB & Van, BC (1986) Influence of dietary nucleotide restriction on bacterial sepsis and phagocytic cell function in mice. Archives of Surgery 121, 169172.Google Scholar
Kulkarni, AD, Rudolph, FB & Van, BC (1994) The role of dietary sources of nucleotides in immune function: a review. Journal of Nutrition 124, 1442S1446S.Google Scholar
Kulkarni, SS, Bhateley, DC, Zander, AR, Van, BC, Rudolph, FB, Dicke, KA & Kulkarni, AD (1984) Functional impairment of T-lymphocytes in mouse radiation chimeras by a nucleotide-free diet. Experimental Hematology 12, 694699.Google Scholar
Lee, TK, Menica Huerta, JM, Shih, C, Corey, EJ, Lewis, RA & Austen, KF (1984) Characterization and biologic properties of 5,12-dihydroxy derivatives of eicosapentaenoic acid, including leukotriene B5 and the double lipoxygebase products. Biological Chemistry 259, 23832389.Google Scholar
LeLeiko, NS, Martin, BA, Walsh, M, Kazlow, P, Rabinowitz, S & Sterling, K (1987) Tissue-specific gene expression results from a purine- and pyrimidine-free diet and 6-mercaptopurine in the rat small intestine and colon. Gastroenterology 93, 10141020.Google Scholar
LeLeiko, NS & Walsh, MJ (1995) Dietary purine nucleotides and the gastrointestinal tract. Nutrition 11, 725730.Google Scholar
Lepoivre, M, Fieschi, F, Coves, J, Thelander, L & Fontecave, M (1991) Inactivation of ribonucleotide reductase by nitric oxide. Biochemical and Biophysical Research Communications 179, 442448.Google Scholar
Li, J, Kudsk, KA, Janu, P & Renegar, KB (1997) Effect of glutamine-enriched total parenteral nutrition on small intestinal gut-associated lymphoid tissue and upper respiratory tract immunity. Surgery 121, 542549.Google Scholar
Lin, E, Goncalves, JA & Lowry, SF (1998) Efficacy of nutritional pharmacology in surgical patients. Current Opinion in Clinical Nutrition and Metabolic Care 1, 4150.Google Scholar
Lokesh, BR & Kinsella, JE (1987) Modulation of prostaglandin synthesis in mouse peritoneal macrophages by enrichment of lipids with either eicospentaenoic or docosahexaenoic acid in vitro. Immunobiology 175, 406419.Google Scholar
Lorente, JA, Landin, L, DePablo, R, Renes, R & Liste, D (1993) L-Arginine pathway in the sepsis syndrome. Critical Care Medicine 21, 12611263.Google Scholar
Lowenstein, CJ, Dinerman, JL & Snyder, SH (1994) Nitric oxide: a physiologic messenger. Annals of Internal Medicine 120, 227237.Google Scholar
Lowry, SF & Thompson, WA (1994) Nutrient modification of inflammatory mediator production. New Horizons 2, 164174.Google Scholar
Martensson, J, Jain, A & Meister, A (1990) Glutathione is required for intestinal function. Proceedings of the National Academy of Sciences USA 87, 17151719.Google Scholar
Mascioli, E, Leader, L, Flores, E, Trimbo, S, Bistrian, B & Blackburn, G (1988) Enhanced survival to endotoxin in guinea pigs fed iv fish oil emulsion. Lipids 23, 623625.Google Scholar
Mendez, C, Jurkovich, GJ, Wener, MH, Garcia, I, Davis, D, Parker, A & Maier, RV (1996) Effects of supplemental dietary arginine, canola oil, and trace elements on cellular immune function in critically injured patients. Journal of Trauma 42, 933941.Google Scholar
Mendez, C, Jurkovich, GJ, Wener, MH, Garcia, I, Mays, M & Maier, RV (1997) Effects of an immune-enhancing diet in critically injured patients. Shock 6, 712.Google Scholar
Meydani, SN, Endres, S, Woods, MM, Goldin, BR, Soo, C, Morrill-Labrode, A, Dinarello, CA & Gorbach, SL (1991) Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. Journal of Nutrition 121, 547555.Google Scholar
Miller, MJ, Zhang, XJ, Sadowska-Krowicka, H, Chotinaruemol, S, McIntyre, JA, Clark, DA & Bustamante, SA (1993) Nitric oxide release in response to gut injury. Scandinavian Journal of Gastroenterology 28, 149154.Google Scholar
Moncada, S, Palmer, RMJ & Higgs, EA (1991) Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacological Reviews 43, 109142.Google Scholar
Moore, FA (1994) Issues in nutritional management of critically ill patients. Nutrition in Clinical Practice 9, 125.Google Scholar
Morlion, BJ, Torwesten, E, Lessire, A, Sturm, G, Peskar, BM, Fürst, P & Puchstein, C (1996) The effect of parenteral fish oil on leukocyte membrane fatty acid composition and leukotriene-synthesizing capacity in postoperative trauma. Metabolism 45, 12081213.Google Scholar
Murphy, MG (1990) Dietary fatty acids and membrane function. Journal of Nutritional Biochemistry 1, 6879.Google Scholar
Nathan, C & Xie, Q (1994) Nitric oxide synthases: rolls, tolls and controls. Cell 78, 915918.Google Scholar
Ninnemann, JL & Stockland, AE (1984) Participation of prostaglandin E in immunosuppression following thermal injury. Journal of Trauma 24, 201207.Google Scholar
Nirgiotis, JG, Hennessey, PJ & Andrassy, RJ (1991) The effects of an arginine-free enteral diet on wound healing and immune function in the postsurgical rat. Journal of Pediatric Surgery 26, 936941.Google Scholar
Nunez, MC, Ayudarte, MV, Morales, D, Suarez, MD & Gil, A (1990) Effect of dietary nucleotides on intestinal repair in rats with experimental chronic diarrhea. Journal of Parenteral and Enteral Nutrition 14, 598604.Google Scholar
Palombo, JD, Bistrian, BR, Fechner, KD, Blackburn, GL & Forse, RA (1993) Rapid incorporation of fish or olive oil fatty acids into rat hepatic sinusoidal cell phospholipids after continuous enteral feeding during endotoxemia. American Journal of Clinical Nutrition 57, 643649.Google Scholar
Parry-Billings, M, Evans, J, Calder, PC & Newsholme, EA (1990) Does glutamine contribute to immunosuppression after major burns? Lancet 336, 523525.Google Scholar
Pizzini, RP, Kumar, S, Kulkarni, AD, Rudolph, FB & Van, BC (1990) Dietary nucleotides reverse malnutrition and starvation-induced immunosuppression. Archives of Surgery 125, 8689.Google Scholar
Pomposelli, JJ, Flores, EA & Bistrian, BR (1988) Role of bio-chemical mediators in clinical nutrition and surgical metabolism. Journal of Parenteral and Enteral Nutrition 12, 212218.Google Scholar
Radomski, MW, Palmer, RM & Moncada, S (1990) An L-arginine/ nitric oxide pathway present in human platelets regulates aggregation. Proceedings of the National Academy of Sciences USA 87, 1004310047.Google Scholar
Rola-Pleszczynski, M & Lemaire, I (1985) Leukotrienes augment interleukin 1 production by human monocytes. Journal of Immunology 135, 39583961.Google Scholar
Rombeau, JL (1990) A review of the effects of glutamine-enriched diets on experimentally induced enterocolitis. Journal of Parenteral and Enteral Nutrition 14, 100S105S.Google Scholar
Ross, JA, Moses, AGW & Fearon, KCH (1999) The anti-catabolic effects of n-3 fatty acids. Current Opinion in Clinical Nutrition and Metabolic Care 2, 219226.Google Scholar
Saffle, JR, Wiebke, G, Jennings, K, Morris, SE & Barton, RG (1997) Randomized trial of immune-enhancing enteral nutrition in burn patients. Journal of Trauma 42, 793800.Google Scholar
Seidner, DL, Mascioli, EA, Istfan, NW, Porter, KA, Selleck, K, Blackburn, GL & Bistrian, BR (1989) Effects of long-chain triglyceride emulsions on reticuloendothelial system function in humans. Journal of Parenteral and Enteral Nutrition 13, 614619.Google Scholar
Senkal, M, Kemen, M, Homann, H-H, Eickhoff, U, Baier, J & Zumtobel, V (1995) Modulation of postoperative immune response by enteral nutrition with a diet enriched with arginine, RNA, and omega-fatty acids in patients with upper gastrointestinal cancer. European Journal of Surgery 161, 115122.Google Scholar
Sodeyama, M, Gardiner, KR, Regan, MC, Kirk, SJ, Efron, G & Barbul, A (1993) Sepsis impairs gut amino acid absorption. American Journal of Surgery 165, 150154.Google Scholar
Souba, WW (1991) Glutamine: a key substrate for the splanchnic bed. Annual Review of Nutrition 11, 285308.Google Scholar
Souba, WW, Klimberg, VS, Hautamaki, RD, Mendenhall, WH, Bova, FC, Howard, RJ, Bland, KI & Copeland, EM III (1990) Oral glutamine reduces bacterial translocation following abdominal radiation. Journal of Surgical Research 48, 15.Google Scholar
Stubbs, CD & Smith, AD (1984) The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochimica et Biophysica Acta 779, 89137.Google Scholar
Szondy, Z & Newsholme, EA (1990) The effect of various concentrations of nucleobases, nucleosides or glutamine on the incorporation of [3H\thymidine into DNA in rat mesenteric-lymph-node lymphocytes stimulated by phytohaemagglutinin. Biochemical Journal 270, 437440.Google Scholar
Terano, T, Salmon, JA & Moncada, S (1984) Biosynthesis and biological activity of leukotriene B5. Prostaglandins 27, 217232.Google Scholar
VanBuren, CT, Kulkarni, AD & Rudolph, FB (1994) The role of nucleotides in adult nutrition. Journal of Nutrition 124, 160S164S.Google Scholar
VanBuren, CT, Kulkarni, AD, Schandle, VB & Rudolph, FB (1983) The influence of dietary nucleotides on cell-mediated immunity. Transplantation 36, 350352.Google Scholar
VanBuren, CT, Rudolph, FB, Kulkarni, A, Pizzini, R, Fanslow, WC & Kumar, S (1990) Reversal of immunosuppression induced by a protein-free diet: comparison of nucleotides, fish oil, and arginine. Critical Care Medicine 18, S114S117.Google Scholar
Wallace, C & Keast, D (1992) Glutamine and macrophage function. Metabolism 41, 10161020.Google Scholar
Watanabe, S, Hayashi, K, Onozaki, K & Okyama, H (1991) Effect of alpha-linolenate/linoleate balance on lipopolysaccharide induced tumor necrosis factor production in mouse macrophages. Life Sciences 48, 20132020.Google Scholar
Windmueller, HG (1982) Glutamine utilization by the small intestine. Advances in Enzymology 53, 201237.Google Scholar
Wink, DA, Kasprzak, KR, Maragos, CM, Elespuru, RK, Misra, M, Dunams, TM, Cebula, TA, Koch, WH, Andrews, AW, Allen, JS & Keefer, LK (1991) DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 254, 10011003.Google Scholar
Wischmeyer, PE, Musch, MW, Madonna, MB, Thisted, R & Chang, EB (1997) Glutamine protects intestinal epithelial cells: Role of inducible HSP70. American Journal of Physiology 272, G879G884.Google Scholar
Wu, D & Meydani, SN (1998) n-3 Polyunsaturated fatty acids and immune function. Proceedings of the Nutrition Society 57, 503509.Google Scholar
Wu, D, Meydani, SN, Meydani, M, Hayek, MG, Huth, P & Nicolosi, RJ (1996) Immunologic effects of marine- and plant-derived n-3 polyunsaturated fatty acids in nonhuman primates. American Journal of Clinical Nutrition 63, 273280.Google Scholar
Yaqoob, P & Calder, P (1995) Effects of dietary lipid manipulation upon inflammatory mediator production by murine macrophages. Cell Immunology 163, 120128.Google Scholar
Yu, JC, Jiang, ZM, Li, DM, Yang, NF & Bai, MX (1996) Alanyl-glutamine preserves hepatic glutathione stores after 5-FU treatment. Clinical Nutrition 15, 261265.Google Scholar
Zaloga, GP (1998) Immune enhancing enteral diets: Where's the beef? Critical Care Medicine 22, 11921202.Google Scholar