Newsletter

[ Vol. 1 No. 2 ] (May - August 2000 )
Glutamine and the Immune Response

Wernerman, Jan
Department of Anaesthesia and Intensive Care, Huddinge University Hospital, S-141 86 Huddinge, Stockholm Sweden.

 In hospital nutrition the focus upon glutamine as a conditionally essential nutrient has evoked a lot of interest recently.  The background is an understanding of glutamine”s role for rapidly diveiding cells such as immunocompetent cells and enterocytes. These cells utilise glutamine as an  oxidative substrate and they prefer glutamine over glucose when both are available, In a situation of stress this preference for glutamine becomes even more evident. The background for this is suggested to be an effective metabolic regulation allowing the production of mucleotides to increase hundred or even thousand fold very rapidly by diverting a small fraction of this flux through the oxidative system. On whole body basis the efflux of glutamine from skeletal muscle, which is the major producer of glutamine, is always evident. Also in the  fed state, when muscle is taking up most of amino acids there is a constant production of glutamine. Skeletal muscle produce glutamine by transamination reactions from other amino acids and by synthesising a ketoglutarate in the TCA-cycle. In metabolic stress the production of glutamine in muscle is enhanced. Muscle is rapidly depleted by this production which for long-stayers in the ICU and during the rehabilitation phase leaves the patient depleted. Although the need for glutamine in the acute situation may be life-saving for the patient, the depletion of muscle proteins may be a serious problem and increase mortality later during the course of disease.

Nutritional supplementation with glutamine may therefore have a rational in the acute situation by improving immunologic competence and gastrointestinal function for the patient ^1,2,3Later on, in the course of disease, glutamine supplementation may save muscle proteins which is shown to be beneficent for the patient during the rehabilitation phase⁴. So far the instrument to diagnose glutamine depletion in individual patients is not at hand. Clinical studies performed are therefore including patients who are glutamine depleted and those who are not glutamine depleted. It is  therefore not surprising that results sometimes are difficult to interpret. In general terms there  are a large number of studies showing a positive nitrogen balance in response to glutamine treatment. Furthermore, in bone marrow transplant patients there is decrease in infectious complications ^5,6, immune cell activation in vitro is enhanced¹and infectious complications following trauma are also attenuated ^7,8 . The latter has been shown also after enteral administration of glutamine. As indicated above, a six-month survival in ICU-patients is also improved by glutamine, an effect that should primarily be attributed to the lower lever of depletion seen in patients after glutamine supplementation of nutrition⁴. The acute effect on the immune response may be more of a pharmacological effect of glutamine. There are convincing experimental evidence on this point, but clinical studies, beside those in bone marrow transplant patients, are presently not at hand.

REFERENCES:
 

1. O’Riordan MG, FearonKC, Ross JA, Rogers P, Falconer JS, Bartolo DCC, Garden OJ, Cater DC. (1994) Glutamine supplemented total parenteral nutrition enhances T-lymphocyte response in surgical patients undergoing colorectal resection. Ann Surg 220-212-221.
2. Hulst RRWJ van der, Kreel BK van, Meyenfeldt MF van, Brummer R-Jm, Arends J-W, Deutz NEP, Soeters PB (1993) The role of parenteral glutamine administration in preserving gut integity, Lancet 334-1363-1365.
3. Tremel H, Kienle B, Weilemann LS, Stehle P, Furst P (1994) Glutamine dipeptide-supplemented parenteral nutrition maintains intesinal function in the critically ill. Gastroenterology 107:1595-1601.
4. Griffiths RD, Jones C, Palmer TEA (1997) A six-month outcome of critically ill patients given glutamine supplemented parenteral nutrition. Nutrition 13:293-302.
5. Ziegler TR, Young LS, Benefell K, Scheltinga M, Hortos K, Bye R, Morrow FD, Jacobs DO, Smith RJ, Antin JH, Wilmore DW (1992) Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. Ann Intern Med 116:821-828.
6. Schloerb PR, Amare M (1993) Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (a randomizd double-blind study). J Parent Enter Nutr 17:407-413.
7. Houdijk APJ, Rijnsburger ER, Jansen J, Wesdorp RIC, Weis JK, McCamish MA, Teerlink T, Meuwissen SGM, Haarman HJTM, Thijs LG, Leeuwen PAM van (1998) Glutamin enriched enteral nutrition reduces infectious morbidity in multi-trauma patients: a double-blind, prospective, randomized trial, Lancet 352:772-776.
8. Moore FA, Moore EE, Kudsk KA, Brown RO, Bower RH, Koruda MJ, Baker CC, Barbul A (1994) Clinical Benefits of an immune-enhancing diet for early postinjury enteral feeding J Trauma 37:607-615.

From
The 5th Congress of the PENSA
October 28-30 1999, Kuala Lumpur.
Page: 27