Glutamine and the immune system

Summary

Glutamine is utilised at a high rate by cells of the immune system in culture and is required to support optimal lymphocyte proliferation and production of cytokines by lymphocytes and macrophages. Macrophage-mediated phagocytosis is influenced by glutamine availability. Hydrolysable glutamine dipeptides can substitute for glutamine to support in vitro lymphocyte and macrophage functions. In man plasma and skeletal muscle glutamine levels are lowered by sepsis, injury, burns, surgery and endurance exercise and in the overtrained athlete. The lowered plasma glutamine concentrations are most likely the result of demand for glutaminne (by the liver, kidney, gut and immune system) exceeding the supply (from the diet and from muscle). It has been suggested that the lowered plasma glutamine concentration contributes, at least in part, to the immunosuppression which accompanies such situations. Animal studies have shown that inclusion of glutamine in the diet increases survival to a bacterial challenge. Glutamine or its precursors has been provided, usually by the parenteral route, to patients following surgery, radiation treatment or bone marrow transplantation or suffering from injury. In most cases the intention was not to stimulate the immune system but rather to maintain nitrogen balance, muscle mass and/or gut integrity. Nevertheless, the maintenance of plasma glutamine concentrations in such a group of patients very much at risk of immunosuppression has the added benefit of maintaining immune function. Indeed, the provision of glutamine to patients following bone marrow transplantation resulted in a lower level of infection and a shorter stay in hospital than for patients receiving glutamine-free parenteral nutrition.

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References

  1. Adjei AA, Matsumoto Y, Oku T, Hiroi Y, Yamamoto S (1994) Dietary arginine and glutamine combination improves survival in septic mice. Nutr Res 14: 1591–1599

    Google Scholar 

  2. Albina JE, Henry W, King PA, Shearer J, Mastrofrancesco B, Goldstein L, Caldwell MD (1987) Glutamine metabolism in rat skeletal muscle wounded withα-carrageenan. Am J Physiol 252: E49–E56

    PubMed  Google Scholar 

  3. Ardawi MSM (1988a) Glutamine and glucose metabolism in human peripheral lymphocytes. Metabolism 37: 99–103

    PubMed  Google Scholar 

  4. Ardawi MSM (1988b) Skeletal muscle glutamine metabolism in thermally-injured rats. Clin Sci 74: 165–172

    PubMed  Google Scholar 

  5. Ardawi MSM (1991) Effect of glutamine-enriched total parenteral nutrition on septic rats. Clin Sci 81: 215–222

    PubMed  Google Scholar 

  6. Ardawi MSM, Newsholme EA (1982) Maxiumum activities of some enzymes of glycolysis, the tricarboxylic acid cycle and ketone body and glutamine utilisation pathways in lymphocytes of the rat. Biochem J 208: 743–748

    PubMed  Google Scholar 

  7. Ardawi MSM, Newsholme EA (1983) Glutamine metabolism in lymphocytes of the rat. Biochem J 212: 835–842

    PubMed  Google Scholar 

  8. Ardawi MSM, Newsholme EA (1985) Metabolism in lymphocytes and its importance in the immune response. Essays Biochem 21: 1–44

    PubMed  Google Scholar 

  9. Ardawi MSM, Majzoub MF (1991) Glutamine metabolism in skeletal muscle of septic rats. Metabolism 40: 155–164

    PubMed  Google Scholar 

  10. Ashworth LAE, MacLennan AP (1974) Comparison of L-asparaginases from Eschericia coli and Erwinia carotovora as immunosuppressants. Cancer Res 34: 1353–1359

    PubMed  Google Scholar 

  11. Askanazi J, Elwyn DH, Kinney JM, Gump FE, Michelsen CB, Stinchfield FE, Furst P, Vinnars E, Bergstrom J (1978) Muscle and plasma amino acids after injury: the role of inactivity. Ann Surg 188: 797–803

    PubMed  Google Scholar 

  12. Askanazi J, Carpentier YA, Michelsen CB, Elwyn DH, Furst P, Kantrowitz LR, Gump FE, Kinney JM (1980) Muscle and plasma amino acids following injury: influence of intercurrent infection. Ann Surg 192: 78–85

    PubMed  Google Scholar 

  13. Bergstrom J, Furst P, Noree L-O, Vinnars E (1974) Intracellular free amino acid concentrations in human skeletal muscle tissue. J Appl Physiol 36: 693–697

    PubMed  Google Scholar 

  14. Brambilla G, Pardodi S, Cavanna M, Caraceni CE, Baldini L (1970) The immunodepressive activity of E. coli L-asparaginase in some transplant systems. Cancer Res 30: 2665–2670

    PubMed  Google Scholar 

  15. Brand K (1985) Glutamine and glucose metabolism during thymocyte proliferation. Biochem J 228: 353–361

    PubMed  Google Scholar 

  16. Brand K, Fekl W, von Hintzenstern J, Langer K, Luppa P, Schoerner C (1989) Metabolism of glutamine in lymphocytes. Metabolism 38: 29–33

    PubMed  Google Scholar 

  17. Calder PC (1994a) Glutamine and the immune system. Clin Nutr 13: 2–8

    Google Scholar 

  18. Calder PC (1994b) Glutamine and the immune system — a reply. Clin Nutr 13: 327–328

    Google Scholar 

  19. Calder PC (1995a) Fuel utilisation by cells of the immune system. Proc Nutr Soc 54: 65–82

    PubMed  Google Scholar 

  20. Calder PC (1995b) Requirement for both glutamine and arginine by proliferating lymphocytes. Proc Nutr Soc 54: 123A

    Google Scholar 

  21. Calder PC, Newsholme EA (1992) Glutamine promotes interleukin-2 production by concanavalin A-stimulated lymphocytes. Proc Nutr Soc 51: 105A

    Google Scholar 

  22. Castell LM, Newsholme EA (1997) The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition 13: 738–742

    PubMed  Google Scholar 

  23. Castell LM, Poortmans JR, Leclercq R, Brasseur M, Duchateau J, Newsholme EA (1997) Some aspects of the acute phase response after a marathon race, and the effects of glutamine supplementation. Eur J Appl Physiol 75: 47–53

    Google Scholar 

  24. Chakrabarti R (1998) Transcriptional regulation of the rat glutamine synthetase gene by tumor necrosis factor-alpha. Eur J Biochem 254: 70–74

    PubMed  Google Scholar 

  25. Chakrabaty AK, Friedman H (1970) L-asparaginase-induced immunosuppression: effects on antibody-forming cells and antibody titres. Science 167: 869–870

    PubMed  Google Scholar 

  26. Chuang JC, Yu CL, Wang SR (1990) Modulation of human lymphocyte proliferation by amino acids. Clin Exp Immunol 81: 173–176

    PubMed  Google Scholar 

  27. Crawford J, Cohen HJ (1985) The essential role of glutamine in lymphocyte differentiation in vitro. J Cell Physiol 124: 275–282

    PubMed  Google Scholar 

  28. Curi TCP, Demelo MP, Deazevedo RB, Zorn TMT, Curi R (1997) Glutamine utilization by rat neutrophils: presence of phosphate-dependent glutaminase. Am J Pbysiol 42: C1124-C1129

    Google Scholar 

  29. Dejong CHC, Heenemann S, Deutz NEP, Buurman WA (1994) Glutamine and the immune system — a reply. Clin Nutr 13: 326–327

    Google Scholar 

  30. Deutz NEP, Heeneman S, van Eijk HMH, Dejong CHC, Mayerink WJHJ, van der Hulst RRWJ, Soeters PB, von Meyenfeldt MF (1992a) Selective uptake of glutamine in the gastrointestinal tract. Br J Surg 79: 280

    PubMed  Google Scholar 

  31. Deutz NEP, Reijven PLM, Athanasas G, Soeters PB (1992b) Post-operative changes in hepatic, intestinal, splenic and muscle fluxes of amino acids and ammonia in pigs. Clin Sci 83: 607–614

    PubMed  Google Scholar 

  32. Durden DL, Distasio JA (1981) Characterisation of the effects of asparaginase from Eschericia coli and a glutaminase-free asparaginase from Vibri succinogenes on specific cell-mediated cytotoxicity. Int J Cancer 27: 59–65

    PubMed  Google Scholar 

  33. Furukawa S, Saito H, Fukatsu K, Hashiguchi Y, Inaba T, Lin M, Inoue T, Han I, Matsuda T, Muto T (1997) Glutamine-enhanced bacterial killing by neutrophils from postoperative patients. Nutrition 13: 863–869

    PubMed  Google Scholar 

  34. Garber AJ (1980) Glutamine metabolism in skeletal muscle. In: Mora J, Palacios R (eds) Glutamine: metabolism, enzymology and regulation. Academic Press, New York, pp 259–284

    Google Scholar 

  35. Griffiths M, Keast D (1990) The effect of glutamine on murine splenic leukocyte responses to T and B cell mitogens. Immunol Cell Biol 68: 405–408

    PubMed  Google Scholar 

  36. Griffiths RD, Jones C, Palmer TEA (1997) Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition 13: 295–302

    PubMed  Google Scholar 

  37. Hack V, Weiss C, Friedmann B, Suttner S, Schykowski M, Erbe N, Benner A, Bartsch P, Droge W (1997) Decreased plasma glutamine level and CD4+ T cell number in response to 8 wk of anaerobic training. Am J Physiol 272: E788–795

    PubMed  Google Scholar 

  38. Hammerqvist F, Wernerman J, von der Decken A, Vinnars E (1990) Alanyl-glutamine counteracts the depletion of free glutamine and post-operative decline in protein synthesis in muscle. Ann Surg 212: 637–645

    PubMed  Google Scholar 

  39. Haussinger D (1989) Glutamine metabolism in the liver: overview and current concepts. Metabolism 38 [Suppl 1]: 14–17

    PubMed  Google Scholar 

  40. Herberer M, Babst R, Juretic A, Gross T, Horig H, Harder F, Spagnoli G (1996) Role of glutamine in the immune response in critical illness. Nutrition 12: S71-S72

    PubMed  Google Scholar 

  41. Hirsch EM (1970) L-glutaminase: suppression of lymphocyte blastogenic responses in vitro. Science 172: 736–738

    Google Scholar 

  42. Houdijk APJ, Rijnsburger ER, Jansen J, Wesdorp RIC, Weis JK, McCamish MA, Teerlink T, Meuwissen SGM, Haarman HJTM, Thijs LG, van Leeuwen RAM (1998) Randomised trial of glutamine-enriched parenteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 352: 772–776

    PubMed  Google Scholar 

  43. Inoue Y, Grant JP, Snyder PJ (1993) Effect of glutamine-supplemented intravenous nutrition on survival afterEscherichia coli-induced peritonitis. JPEN 17: 41–46

    Google Scholar 

  44. Jensen GL, Miller RH, Talabiska DG, Fish J, Gianferante L (1996) A double blind, prospective, randomized study of glutamine-enriched compared with standard peptide-based feeding in critically ill patients. Am J Clin Nutr 64: 615–621

    PubMed  Google Scholar 

  45. Kafkewitz D, Bendich A (1983) Enzyme-induced asparagine and glutamine depletion and immune system dysfunction. Am J Clin Nutr 37: 1025–1030

    PubMed  Google Scholar 

  46. Keast D, Newsholme EA (1990) Effect of mitogens on the maximum activities of hexokinase, lactate dehydrogenase, citrate synthase and glutaminase in rat mesenteric lymph node lymphocytes and splenocytes during the early period of culture. Int J Biochem 22: 133–136

    PubMed  Google Scholar 

  47. Keast D, Arstein DL, Harper W, Fry RW, Morton AR (1995) Depression of plasma glutamine concentration after exercise stress and its possible influence on the immune system. Med J Aust 162: 15–18

    PubMed  Google Scholar 

  48. Kew S, Wells SM, Yaqoob P, Wallace FA, Miles EA, Calder PC (1999) Dietary glutamine enhances murine T-lymphocyte responsiveness. J Nutr 129: 1524–1531

    PubMed  Google Scholar 

  49. Kweon MN, Moriguchi S, Mukai K, Kishino Y (1991) Effect of alanylglutamine-enriched infusion on tumour growth and cellular immune function in rats. Amino Acids 1: 7–16

    Google Scholar 

  50. Lacey JM, Wilmore DW (1990) Is glutamine a conditionally essential amino acid? Nutr Rev 48: 297–309

    PubMed  Google Scholar 

  51. Lowe DK, Benfell K, Smith RJ, Jacobs DO, Murawski B, Ziegler TR, Wilmore DW (1990) Safety of glutamine-enriched parenteral nutrient solutions in humans. Am J Clin Nutr 52: 1101–1106

    PubMed  Google Scholar 

  52. Lund J, Stjernstrom H, Bergholm U, Jorfeldt L, Vinnars E, Wiklund L (1986) The exchange of blood-borne amino acids in the leg during abdominal surgical trauma: effects of glucose infusion. Clin Sci 71: 487–496

    PubMed  Google Scholar 

  53. Lund P (1981) Metabolism of glutamine, glutamate and aspartate. In: Waterlow JC, Stephen JML (eds) Nitrogen metabolism in man. Applied Sciences, London, pp 155–167

    Google Scholar 

  54. Lund P, Williamson DH (1985) Inter-tissue nitrogen fluxes. Br Med Bull 41: 251–256

    PubMed  Google Scholar 

  55. Max SR, Hill J, Mearow K, Konagaya H, Konagaya Y, Thomas JW, Banner C, Vitkavic L (1988) Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles. Am J Physiol 255: E397–E403

    PubMed  Google Scholar 

  56. Meister A (1956) Metabolism of glutamine. Physiol Rev 36: 103–127

    PubMed  Google Scholar 

  57. Milewski PJ, Threlfall CJ, Heath DF, Holbrook JB, Wilford K, Irving MH (1982) Intracellular free amino acids in undernourished patients with and without sepsis. Clin Sci 62: 83–91

    PubMed  Google Scholar 

  58. Morlion BJ, Stehle P, Wachter P, Siedhoff HP, Koller M, Konig W, Furst P, Puchstein C (1998) Total parenteral nutrition with glutamine dipeptide after major abdominal surgery — a randomized, double-blind, controlled study. Ann Surg 227: 302–308

    PubMed  Google Scholar 

  59. Muhlbacher F, Kapadia CR, Colpoys MF, Smith RJ, Wilmore DW (1984) Effects of glucocorticoids on glutamine metabolism in skeletal muscle. Am J Physiol 247: E75-E83

    PubMed  Google Scholar 

  60. Murphy C, Newsholme P (1999) Macrophage-mediated lysis of aβ-cell line, tumour necrosis factor-a release from bacillus Calmette-Guerin (BCG)-activated murine macrophages and interleukin-8 release from human monocytes are dependent on extracellular glutamine concentrastion and glutamine metabolism. Clin Sci 96: 89–97

    PubMed  Google Scholar 

  61. Naka S, Saito H, Hashiguchi Y, Lin MT, Furukawa S, Inoba T, Fukushima R, Wada N, Muto T (1996) Alanyl-glutamine-supplemented total parenteral nutrition improves survival and protein metabolism in rat protracted bacterial peritonitis model. JPEN 20: 417–423

    Google Scholar 

  62. Neu J, Roig JC, Meetze WH, Veerman M, Cater C, Millsaps M, Bowling D, Dallas MJ, Sleasman J, Knight T, Anestad N (1997) Enteral glutamine supplementation for very low birthweight infants decreases morbidity. J Pediatr 131: 691–699

    PubMed  Google Scholar 

  63. Newsholme EA, Newsholme P, Curi R, Crabtree B, Ardawi MSM (1989) Glutamine metabolism in different tissues: its physiological and pathological importance. In: Kinney JM, Borum PR (eds) Perspectives in clinical nutrition. Urban and Schwarzenberg, Baltimore, pp 71–98

    Google Scholar 

  64. Newsholme P, Newsholme EA (1989) Rates of utilisation of glucose, glutamine and oleate and formation of end products by mouse peritoneal macrophages in culture. Biochem J 261: 211–218

    PubMed  Google Scholar 

  65. Newsholme P, Curi R, Cordon S, Newsholme EA (1986) Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages. Biochem J 239: 121–125

    PubMed  Google Scholar 

  66. Newsholme P, Gordon S, Newsholme EA (1987) Rates of utilisation and fates of glucose, glutamine, pyruvate, fatty acids and ketone bodies by mouse macrophages. Biochem J 242: 631–636

    PubMed  Google Scholar 

  67. Ogle CK, Ogle JD, Mao JX, Simon J, Noel JG, Li BG, Alexander JW (1994) Effect of glutamine on phagocytosis and bacterial killing by normal and pediatric burn patient neutrophils. JPEN 18: 128–133

    Google Scholar 

  68. O'Riordain M, Fearon KC, Ross JA, Rogers P, Falconer JS, Bartolo DCC, Garden OJ, Carter DC (1994) Glutamine supplemented parenteral nutrition enhances Tlymphocyte response in surgical patients undergoing colorectal resection. Ann Surg 220: 212–221

    PubMed  Google Scholar 

  69. O'Rourke AM, Rider LC (1989) Glucose, glutamine and ketone body utilisation by resting and concanavalin a activated rat splenic lymphocytes. Biochem Biophys Acta 1010: 342–345

    PubMed  Google Scholar 

  70. Parry-Billings M, Leighton B, Dimitriadis GD, de Vasconcelos PRL, Newsholme EA (1989) Skeletal muscle glutamine metabolism during sepsis. Int J Biochem 21: 419–423

    PubMed  Google Scholar 

  71. Parry-Billings M, Evans J, Calder PC, Newsholme EA (1990a) Does glutamine contribute to immunosuppression after major burns? Lancet 336: 523–525

    PubMed  Google Scholar 

  72. Parry-Billings M, Leighton B, Dimitriadis GD, Bond J, Newsholme EA (1990b) Effects of physiological and pathological levels of glucocorticoids on skeletal muscle glutamine metabolism in the rat. Biochem Pharmacol 40: 1145–1148

    PubMed  Google Scholar 

  73. Parry-Billings M, Leighton B, Dimitriadis G, Curi R, Bond J, Bevan S, Colquhoun A, Newsholme EA (1991) The effect of tumour bearing on skleletal muscle glutamine metabolism. Int J Biochem 23: 933–937

    PubMed  Google Scholar 

  74. Parry-Billings M, Baigrie RJ, Lamont PM, Morris PJ, Newsholme EA (1992a) Effects of major and minor surgery on plasma glutamine and cytokine levels. Arch Surg 127: 1237–1240

    PubMed  Google Scholar 

  75. Parry-Billings M, Budgett R, Koutedakis Y, Blomstrand E, Williams C, Calder PC, Pilling S, Baigrie R, Newsholme EA (1992b) Plasma amino acid concentrations in the overtraining syndrome: possible effects on the immune system. Med Sci Sports Exerc 24: 1353–1358

    PubMed  Google Scholar 

  76. Peltonen E, Pulkki K, Kirvela O (1997) Stimulatory effect of glutamine on human monocyte activation as measured by interleukin-6 and soluble interleukin-6 receptor release. Clin Nutr 16: 125–128

    Google Scholar 

  77. Powell H, Castell LM, Parry-Billings M, Desborough JP, Hall GM, Newsholme EA (1994) Growth hormone suppression and glutamine flux associated with cardiac surgery. Clin Physiol 14: 569–580

    PubMed  Google Scholar 

  78. Rohde T, Maclean DA, Hartkopp A, Pedersen BK (1996a) The immune system and serum glutamine during a triathalon. Eur J Appl Physiol 74: 428–434

    Google Scholar 

  79. Rohde T, Maclean DA, Pedersen BK (1996b) Glutamine, lymphocyte proliferation and cytokine production. Scand J Immunol 44: 648–650

    PubMed  Google Scholar 

  80. Roth E, Funovics J, Muhlbacher F, Schemper M, Mauritz W, Sporn P, Fritsch A (1982) Metabolic disorders in severe abdominal sepsis: glutamine deficiency in skeletal muscle. Clin Nutr 1: 25–41

    Google Scholar 

  81. Scheltinga MR, Young LS, Benfell K, Bye RL, Ziegler TR, Santos AA, Antin JH, Schloerb PR, Wilmore DW (1991) Glutamine-enriched intravenous feedings attenuate extracellular fluid expansion after standard stress. Ann Surg 214: 385–395

    PubMed  Google Scholar 

  82. Schroder J, Lahlke V, Fandrich F, Gebhardt H, Erichsen H, Zabel P, Schroeder P (1998) Glutamine dipeptides-supplemented parenteral nutrition reverses gut muscosal structure and interleukin-6 release of rat intestinal mononuclear cells after hemorrhagic shock. Shock 10: 26–31

    PubMed  Google Scholar 

  83. Shewchuk LD, Baracos VE, Field CJ (1997) Dietary L-glutamine supplementation reduces growth of the Morris Hepatoma 7777 in exercise-trained and sendentary rats. J Nutr 127: 158–166

    PubMed  Google Scholar 

  84. Simberkoff MS, Thomas L (1970) Reversal by L-glutamine of the inhibition of lymphocyte mitosis caused by E. coli asparaginase. Proc Soc Exp Biol 133: 642–643

    Google Scholar 

  85. Smith KA (1988) Interleukin-2: inception, impact and implications. Science 240: 1169–1176

    PubMed  Google Scholar 

  86. Souba WW, Smith RJ, Wilmore DW (1985) Glutamine metabolism in the intestinal tract. JPEN 9: 608–617

    Google Scholar 

  87. Souba WW, Klimberg VS, Hautamaki RD, Mendenhall WH, Bova FC, Howard RJ, Bland KI, Copeland III EM (1990) Oral glutamine reduces bacterial translocation following abdominal radiation. J Surg Res 48: 1–5

    PubMed  Google Scholar 

  88. Spittler A, Winkler S, Gotzinger P, Oehler R, Willheim M, Tempfer C, Weigel G, Fugger R, Boltz-Nitulescu G, Roth E (1995) Influence of glutamine on the phenotype and function of human monocytes. Blood 86: 1564–1569

    PubMed  Google Scholar 

  89. Spittler A, Holzer S, Oehler R, Boltz-Nitulescu G, Roth E (1997) A glutamine deficiency impairs the function of cultured human monocytes. Clin Nutr 16: 97–99

    Google Scholar 

  90. Stehle P, Zander J, Mertes N, Albers S, Puchstein C, Lavin P, Furst P (1989) Effect of parenteral glutamine dipeptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet i: 231–233

    Google Scholar 

  91. Stinnett JD, Alexander JW, Watanabe C, Elwyn DH, Furst P, Kantrowitz LR, Gump FE, Kinney JM (1982) Plasma and skeletal muscle amino acids following severe burn injury in patients and experimental animals. Ann Surg 195: 75–89

    PubMed  Google Scholar 

  92. Suzuki I, Matsumoto Y, Adjei AA, Osato L, Shinjo S, Yamamoto S (1993) Effect of a glutamine-supplemented diet in response to methicellin-resistantStaphylococcus aureus infection in mice. J Nutr Sci Vitaminol 39: 405–410

    PubMed  Google Scholar 

  93. Szondy Z, Newsholme EA (1989) The effect of glutamine concentration on the activity of carbamoyl-phosphate synthase II and on the incorporation of [3H]thymidine into DNA in rat mesenteric lymphocytes stimulated by phytohaemagglutinin. Biochem J 261: 979–983

    PubMed  Google Scholar 

  94. Tizianello A, Deferrari G, Garibotto G, Robabaudo C, Asquarone N, Ghiggeri GN (1982) Renal ammoniagenesis in an early stage of metabolic acidosis in man. J Clin Invest 69: 240–250

    PubMed  Google Scholar 

  95. van der Hulst RRW, van Kreel BK, von Meyenfeldt MF, Brummer R-JM, Arends J-W, Deutz NEP, Soeters PB (1993) Glutamine and the preservation of gut integrity. Lancet 341: 1363–1365

    PubMed  Google Scholar 

  96. Wallace C, Keast D (1992) Glutamine and macrophage function. Metabolism 41: 1016–1020

    PubMed  Google Scholar 

  97. Wells SM, Kew S, Yaqoob P, Wallace FA, Calder PC (1999) Dietary glutamine enhances cytokine production by murine macrophages. Nutrition (in press)

  98. Windmeuller HG, Spaeth AE (1974) Uptake and metabolism of plasma glutamine by the small intestine. J Biol Chem 249: 5070–5079

    PubMed  Google Scholar 

  99. Yoshida S, Hikida S, Tanaka Y, Yanase A, Mizote H, Kaegawa T (1992) Effect of glutamine supplementation on lymphocyte function in septic rats. JPEN 16: 30S

    Google Scholar 

  100. Yaqoob P, Calder PC (1997) Glutamine requirement of proliferating T lymphocytes. Nutrition 13: 646–651

    PubMed  Google Scholar 

  101. Yaqoob P, Calder PC (1998) Cytokine production by human peripheral blood mononuclear cells: differential sensitivity to glutamine availability. Cytokine 10: 790–794

    PubMed  Google Scholar 

  102. Yoo SS, Field CJ, McBurney MI (1997) Glutamine supplementation maintains intramuscular glutamine concentrations and normalizes lymphocyte function in infected early weaned pigs. J Nutr 127: 2253–2259

    PubMed  Google Scholar 

  103. Ziegler TR, Bye RL, Persinger RL, Young LS, Antin JH, Wilmore DW (1998) Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: A pilot study. Am J Med Sci 315: 4–10

    PubMed  Google Scholar 

  104. Ziegler TR, Young LS, Benfell K, Scheltinga M, Hortog K, Bye R, Morrow FD, Jacobs DO, Smith RJ, Antin JH, Wilmore DW (1992) Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition following bone marrow transplantation: a double-blinded, randomized, controlled trial. Ann Intern Med 116: 821–828

    PubMed  Google Scholar 

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Calder, P.C., Yaqoob, P. Glutamine and the immune system. Amino Acids 17, 227–241 (1999). https://doi.org/10.1007/BF01366922

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Keywords

  • Amino acids
  • Glutamine
  • Lymphocyte
  • Macrophage
  • Mononuclear cell
  • Cytokine
  • Infection