Effect of Exogenous Glutamine on Immune Function and Survival in Animal Models of Infection and Trau

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A number of animal studies have been performed to investigate the effect of glutamine on the ability to withstand challenges with various pathogens or tumour bearing. Glutamine-supplemented parenteral nutrition improved survival (75% vs. 45% in the control group receiving standard parenteral nutri tion) in rats following caecal ligation and puncture (Ardawi, 1991). Likewise, intravenous glutamine improved survival (92% vs. 55% in the control group) following an intraperitoneal injection of live Escherichia coli into rats (Inoue et al., 1993). Parenteral administration of alanyl-glutamine into rats improved survival (86% vs. 44% in the control group) in response to intraperitoneally infused E. coli (Naka et al., 1996). Suzuki et al. (1993) fed mice for 10 days on diets containing casein or casein supplemented with 20 g or 40 g gluta-mine kg-1 and then inoculated them intravenously with live Staphylococcus aureus. Over the following 20 days, during which the mice were maintained on the same diets they had been fed prior to infection, 80% of the control animals died, while mortality was 60% in the 20 g glutamine kg-1 group and 30% in the 40 g glutamine kg-1 group. Another study showed that inclusion of glutamine in parenteral nutrition decreased mortality to intratracheally inoculated Pseudomonas (23% and 30% mortality at 24 and 48 h in the glut-amine group vs. 55% and 75% mortality at 24 and 48 h in the control group) (DeWitt et al., 1999). In addition to enhanced survival, these studies showed that glutamine improved nitrogen balance diminished the sepsis-induced decrease in muscle glutamine concentration and decreased muscle protein breakdown (Ardawi, 1991), increased plasma glutamine concentration (Inoue et al., 1993), increased intestinal function and/or integrity (Inoue et al., 1993; Naka et al., 1996), and enhanced muscle protein synthesis (Ardawi, 1991; Naka et al., 1996). These studies did not measure indices of immune function. However, Yoo et al. (1997) reported that proliferation of blood lymphocytes from E. coli-infected piglets was significantly higher if the piglets consumed a diet containing 40 g glutamine kg-1 compared with a diet that did not contain glutamine. Shewchuk et al. (1997) reported that Con A-stim-ulated proliferation of spleen lymphocytes taken from tumour-bearing rats fed a diet containing an increased amount of glutamine was greater than that of those taken from rats fed a standard casein-containing diet. Furthermore, infusion of alanyl-glutamine into tumour-bearing rats increased the in vitro phagocytic capacity of alveolar macrophages (Kweon et al., 1991), while infusion into septic rats increased in vitro proliferation of mitogen-stimulated blood lymphocytes (Yoshida et al., 1992). These studies indicate that provision of glutamine either parenterally or enterally increases the function of various immune cells and that this might account for the enhanced resistance to infection observed in other studies.

A series of studies has examined the influence of glutamine on the gut-associated and respiratory lymphoid systems in mice undergoing various challenges. Parenteral glutamine or alanyl-glutamine maintained the lymphocyte yield from Peyer's patches and intestinal integrity in mice given an intranasal inoculation of influenza virus (Li et al., 1997, 1998). More recently, enteral glutamine was found to increase total cellularity of Peyer's patches (and spleen) in LPS-treated mice (Manhart et al., 2000); this effect was mainly due to an increase in T-cell number. In another recent study, inclusion of glutamine in parenteral nutrition improved the concentration of secretory immunoglobulin A in the intestinal lumen and improved intestine IL-4 and IL-10 concentrations (Kudsk et al., 2000).

In an animal model of haemorrhagic shock, standard parenteral nutrition decreased the ex vivo release of TNF-a and IL-6 by LPS-stimulated gut mononuclear cells and spleen macrophages and was associated with injury to the gut mucosa and bacterial translocation into the mesenteric lymph nodes (Schroder et al., 1998). Inclusion of alanyl-glutamine and glycyl-glutamine in the parenteral regimen improved mucosal structure and prevented the fall in ex vivo IL-6, but not TNF-a, release (Schroder et al., 1998).

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How To Bolster Your Immune System

How To Bolster Your Immune System

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