Effects of oral supplementation with glutamine and alanyl-glutamine on glutamine,glutamate, and glutathione status in trained rats and subjected to long-duration exercise

ObjectiveWe investigated the effect of supplementation with the dipeptide L-alanyl-L-glutamine (DIP) and a solution containing L-glutamine and L-alanine, both in the free form, on the plasma and tissue concentrations of glutamine, glutamate, and glutathione (GSH) in rats subjected to long-duration exercise.MethodsRats were subjected to sessions of swim training. Twenty-one days before sacrifice, the animals were supplemented with DIP (1.5 g/kg, n = 6), a solution of free L-glutamine (1 g/kg) and free L-alanine (0.61 g/kg; GLN + ALA, n = 6), or water (CON, n = 6). Animals were sacrificed before (TR, n = 6) or after (LD, n = 6) long-duration exercise. Plasma concentrations of glutamine, glutamate, glucose, and ammonia and liver and muscle concentrations of glutamine, glutamate, and reduced and oxidized (GSSG) GSH were measured.ResultsHigher concentrations of plasma glutamine were found in the DIP-TR and GLN + ALA-TR groups. The CON-LD group showed hyperammonemia, whereas the DIP-LD and GLN + ALA-LD groups exhibited lower concentrations of ammonia. Higher concentrations of glutamine, glutamate, and GSH/GSSG in the soleus muscle and GSH and GSH/GSSG in the liver were observed in the DIP-TR and GLN + ALA-TR groups. The DIP-LD and GLN + ALA-LD groups exhibited higher concentrations of GSH and GSH/GSSG in the soleus muscle and liver compared with the CON-LD group.ConclusionChronic oral administration of DIP and free GLN + ALA before long-duration exercise represents an effective source of glutamine and glutamate, which may increase muscle and liver stores of GSH and improve the redox state of the cell.     

Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants

BACKGROUND: Glutamine is one of the most abundant amino acids in both plasma and human milk and may be conditionally essential in premature infants. However, glutamine is not provided by standard intravenous amino acid solutions. OBJECTIVE: We assessed the effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants receiving parenteral nutrition (PN). DESIGN: A total of 141 infants with birth weights of 401-1000 g were randomly assigned to receive a standard intravenous amino acid solution that did not contain glutamine or an isonitrogenous amino acid solution with 20% of the total amino acids as glutamine. Blood samples were obtained just before initiation of study PN and again after the infants had received study PN (mean intake: 2.3 +/- 1.0 g amino acids x kg(-1) x d(-1)) for approximately 10 d. RESULTS: Infants randomly assigned to receive glutamine had mean plasma glutamine concentrations that increased significantly and were approximately 30% higher than those in the control group in response to PN (425 +/- 182 and 332 +/- 148 micromol/L for the glutamine and control groups, respectively). There was no significant difference between the 2 groups in the relative change in plasma glutamate concentration between the baseline and PN samples. In both groups, there were significant decreases in plasma phenylalanine and tyrosine between the baseline and PN samples; the decrease in tyrosine was greater in the group that received glutamine. CONCLUSIONS: In extremely low-birth-weight infants, parenteral glutamine supplementation can increase plasma glutamine concentrations without apparent biochemical risk. Currently available amino acid solutions are likely to be suboptimal in their supply of phenylalanine, tyrosine, or both for these infants.     

Dietary glutamine supplementation reduces plasma nitrate levels in rats

It was recently shown that L-glutamine inhibits vascular nitric oxide (NO) production in vitro. The present study investigated the effect of glutamine enriched enteral diets on in vivo NO production in the rat. Nitrate, the stable end-product of NO production, was measured in plasma and 24 h urine collections in glutamine supplemented rats (6.25%, 12.5% and 25% w/w) and compared to the effect of isocaloric, nitrogenous control diets. Glutamine supplementation increased plasma levels of glutamine (up to 91%), arginine (up to 17%) and citrulline (up to 54%). After 1 week of glutamine supplementation plasma nitrate levels were significantly reduced by 50% compared to control (P < 0. 0001); irrespective of the amount of supplementation. No further decrease was observed after 2 weeks of feeding. No differences in daily urinary losses were found between the groups. These results point to an in vivo inhibitory effect of glutamine supplemented enteral feeding on NO production.     

Changes in plasma zinc and folic acid concentrations in pregnant adolescents submitted to different supplementation regimens

Zinc and folic acid nutritional status was evaluated in 74 low-income pregnant adolescents ranging from 13 to 18 years of age who received prenatal care at the Evangelina Rosa Maternity Hospital in Teresina, Piau State, Brazil. In order to evaluate the effects of different supplementation regimens on nutritional status, the adolescents were distributed into five groups. Groups I and II received equal amounts of folic acid (250 micro;g) and different doses of iron (ferrous sulfate), 120 and 80 mg, respectively. Groups III and IV received equal amounts of folic acid (250 micro;g) associated with zinc sulfate and iron at doses of 120 and 80 mg, respectively, while group V received only 120 mg of iron (routine dosage). There was a reduction in the zinc plasma concentration, and this decline was significant only in those groups which did not receive zinc supplementation. In relation to combination iron/folic acid and iron/folic acid/zinc, an excellent response was observed for folic acid, and this effect was larger in the groups that received folic acid combined with zinc, suggesting a possible role for zinc in folic acid metabolism.     

Effect of glutamine supplementation of the diet on tissue protein synthesis rate of glucocorticoid-treated rats

Although glutamine status in the critically ill patient can be improved by nutritional means, the most effective way of effecting such supplementation has received little attention. We evaluated two different ways of supplementing clinical nutrition products with glutamine, either with free glutamine or by providing a glutamine-rich protein source, in acute glucocorticoid-treated (intraperitoneal dexamethasone, 120 mg/kg) rats. During the recovery period, the animals received isonitrogenous and isoenergetic diets containing either casein, mixed whey proteins with or without glutamine, or carob protein plus essential amino acids. Plasma and tissue amino acids and glutathione as well as tissue protein synthesis were measured. Dexamethasone treatment lowered weight gain, muscle glutamine, and muscle and jejunal protein synthetic rate. Muscle protein synthesis was increased (from 15.9% to 24.2%/d) only when glutamine was included in the diet as a free amino acid. This increase paralleled a rise in plasma glutamine. We speculate that glutamine provided in dietary protein is extensively metabolized by the splanchnic tissues and does not influence peripheral glutamine status to the same extent as glutamine provided in a free amino acid form. However, both forms of glutamine supplementation were equally effective in increasing protein synthesis in the jejunum (by 25%). This is likely the main benefit of glutamine supplementation of enteral nutrition formulas.     

Effect of glutamine supplementation on protein metabolism and glutathione in tumor-bearing rats

The effect of glutamine (GLN)-supplemented total parenteral nutrition (TPN) on tumor growth and protein metabolism was investigated in tumor-bearing rats. Six days after implantation of AH109A hepatoma, rats received isonitrogenous TPN without or with alanyl-glutamine (25% of total N) for a period of 6 days. Protein turnover was assessed by continuous infusion of l4C-leucine and levels of GLN and glutathione were determined in muscle, jejunum and liver. Diet had no effect on tumor parameters: weight (mean = 4.4 g), GLN and glutathione concentrations, protein synthesis rate and bromodeoxyuridine-labeling index. Body weight loss was less pronounced in the GLN group (-5.5 +/- 1.2 vs. -9.4 +/- 1.4 g/5d). Decrease in plasma and muscle GLN concentrations (-30% and -17% vs. healthy controls, respectively) was limited in tumor-bearing rats receiving GLN-enriched TPN (-15% and +3%). GLN-supplemented TPN increased muscle and jejunum fractional synthesis rates (36% and 25% vs. standard TPN, respectively) and reduced body protein breakdown in tumor-bearing animals (303 +/- 33 vs. 421 +/- 66 mumol Leu/Kg/h). Decrease in jejunum glutathione levels was partially abolished in the GLN group: -50% vs. -64% in the standard TPN group; no effect was noticed in other tissues. The authors conclude that GLN-supplemented TPN improves protein metabolism at both the whole body and the tissue level, and prevents GLN and glutathione deficiencies associated with tumor implantation.     

Plasma taurine concentrations increase after enteral glutamine supplementation in trauma patients and stressed rats

BACKGROUND: Taurine is a unique amino acid with antioxidant and osmolytic properties. Glutamine serves as the preferred fuel for the gut, liver, and immune cells and as a precursor for antioxidants. Trauma patients have low glutamine concentrations. OBJECTIVES: We investigated the effect of glutamine-enriched enteral nutrition on plasma taurine concentrations in patients with severe trauma (injury severity score >20). Additionally, plasma taurine concentrations and organ fluxes were studied in a stressed rat model. DESIGN: Twenty-nine patients with multiple trauma received glutamine-enriched nutrition and 31 patients received isocaloric, isonitrogenous control solution for 5 d. Plasma taurine and glutamine concentrations were measured. Male Wistar rats (250-300 g) received a glutamine-enriched diet (12%, by wt) or a control solution for 2 wk. Plasma taurine concentrations were measured. Taurine fluxes and fractional extraction rates in the liver, kidneys, and gut were assessed with a radioactive microsphere technique. RESULTS: Both patient groups had low taurine concentrations on day 1. From day 3 onward, the glutamine-fed patients had significantly higher taurine concentrations. Rats fed a glutamine-enriched diet had significantly higher plasma taurine concentrations than did the controls. A high taurine uptake was found in the liver, kidneys, and gut of the glutamine-fed rats. Fractional extraction rates were not significantly different between the rat groups. CONCLUSIONS: Glutamine enrichment increases plasma taurine in trauma patients and in stressed rats. Because of increased availability, organ fluxes showed a higher taurine uptake in the liver, kidneys, and gut. The reduction in morbidity with glutamine enrichment could be explained in part by increased taurine availability.     

Effect of oral glutamine supplementation on human neutrophil lipopolysaccharide-stimulated degranulation following prolonged exercise

Recent studies have shown that neutrophils can utilize glutamine and that glutamine supplementation can improve neutrophil function in postoperative and burn patients. The present study investigated the influence of oral glutamine supplementation on stimulated neutrophil degranulation and oxidative burst activity following prolonged exercise. Subjects, 7 well-trained men, reported to the laboratory following an overnight fast and cycled for 2 hrs at 60% VO2max on two occasions a week apart. They were randomly assigned to either a glutamine or placebo treatment. For both trials, subjects consumed a sugar-free lemon drink at 15-min intervals until 90 minutes, then a lemon flavored glutamine drink (GLN) or sugar-free lemon drink (PLA) was consumed at 15-min intervals for the remaining exercise and the 2-hr recovery period. Venous blood samples were taken pre-, during, and postexercise. Glutamine supplementation had no effect on the magnitude of postexercise leukocytosis, the plasma elastase concentration following exercise (which increased in both trials), or the plasma elastase release in response to bacterial stimulation (which fell in both trials). Neutrophil function assessed by oxidative burst activity of isolated cells did not change following exercise in either trial. These findings therefore suggest that the fall in plasma glutamine concentration does not account for the decrease in neutrophil function (degranulation response) following prolonged exercise.     

力竭运动致大鼠心肌组织损伤后p53蛋白表达变化

目的观察p53蛋白在力竭运动损伤大鼠心肌组织中的表达变化。方法 Wistar大鼠12只,随机分为对照(C)组和力竭运动损伤(EI)组。EI组大鼠进行梯度负荷的跑台运动至力竭,共训练10 d;取血测定丙二醛(MDA)水平及超氧化物歧化酶(SOD)活力等;用光镜和电镜对心肌进行组织学观察;采用Western-blot和免疫组织化学法检测p53蛋白表达。结果力竭运动后,大鼠血液中乳酸脱氢酶(LDH)活力升高;一氧化氮(NO)水平降低;MDA水平升高;同时SOD活力下降。心肌组织苏木素-伊红染色法染色可见,大鼠心肌和血管内皮细胞空泡变性和心肌间质水肿等;电镜可见,血管内皮细胞发生典型细胞凋亡特征。Western-blot结果表明,C组心肌组织中p53蛋白仅极少量表达,而EI组心肌中p53蛋白表达水平升高;免疫组织化学结果显示,与C组比较,EI组心肌中p53蛋白表达升高,且在心肌和内皮细胞中均有表达。结论力竭运动不仅可致心肌氧化应激损伤,还可诱发大鼠心血管内皮细胞凋亡。p53蛋白在力竭运动损伤心肌组织中表达升高。     

Carbohydrate supplementation and immune responses after acute exhaustive resistance exercise

This investigation sought to study changes in leukocyte subsets after an acute bout of resistance exercise (ARE) and to determine whether ingestion of carbohydrate (CHO) could attenuate those immune responses. Nine male track-and-field athletes (21.1 +/- 1.4 yr, 177.2 +/- 5.5 cm, 80.9 +/- 9.7 kg, 8.7% +/- 3.8% fat) and 10 male ice hockey athletes (21.0 +/- 2.2 yr, 174.3 +/- 6.2 cm, 79.6 +/-11.1 kg, 13.9% +/- 3.73% fat) participated in 2 different ARE protocols. Both experiments employed a counterbalanced double-blind research design, wherein participants consumed either a CHO (1 g/kg body weight) or placebo beverage before, during, and after a weight-lifting session. Serum cortisol decreased (p < .05) at 90 min into recovery compared with immediately postexercise. Plasma lactate, total leukocyte, neutrophil, and monocyte concentrations increased (p < .05) from baseline to immediately postexercise. Lymphocytes decreased significantly (p < .05) from baseline to 90 min postexercise. Lymphocytes were lower (p < .05) for the CHO condition than for placebo. The findings of this study indicate the following: ARE appears to evoke changes in immune cells similar to those previously reported during endurance exercise, and CHO ingestion attenuates lymphocytosis after ARE.     

Lycopene supplementation attenuated xanthine oxidase and myeloperoxidase activities in skeletal muscle tissues of rats after exhaustive exercise

Strenuous exercise is known to induce oxidative stress leading to the generation of free radicals. The purpose of the present study was to investigate the effects of lycopene, an antioxidant nutrient, at a relatively low dose (2.6 mg/kg per d) and a relatively high dose (7.8 mg/kg per d) on the antioxidant status of blood and skeletal muscle tissues in rats after exhaustive exercise. Rats were divided into six groups: sedentary control (C); sedentary control with low-dose lycopene (CLL); sedentary control with high-dose lycopene (CHL); exhaustive exercise (E); exhaustive exercise with low-dose lycopene (ELL); exhaustive exercise with high-dose lycopene (EHL). After 30 d, the rats in the three C groups were killed without exercise, but the rats in the three E groups were killed immediately after an exhaustive running test on a motorised treadmill. The results showed that xanthine oxidase (XO) activities of plasma and muscle, and muscular myeloperoxidase (MPO) activity in group E were significantly increased compared with group C. Compared with group E, the elevations of XO and MPO activities of muscle were significantly decreased in group EHL. The malondialdehyde concentrations of plasma and tissues in group E were significantly increased by 72 and 114 %, respectively, compared with those in group C. However, this phenomenon was prevented in rats of the ELL and EHL groups. There was no significant difference in the GSH concentrations of erythrocytes in each group; however, exhaustive exercise resulted in a significant decrease in the GSH content of muscle. In conclusion, these results suggested that lycopene protected muscle tissue from oxidative stress after exhaustive exercise.     

Effect of alanyl-glutamine on leucine and protein metabolism in endotoxemic rats

BACKGROUND: Branched-chain amino acids (BCAA; valine, leucine, and isoleucine) have a regulatory effect on protein metabolism and are the main donor for synthesis of alanine and glutamine in the skeletal muscle. This study was performed to investigate whether exogenous alanine or glutamine would affect leucine and protein metabolism in intact and endotoxemic rats. METHODS: Rats were injected with endotoxin of Salmonella enteritidis or saline. Thirty minutes later, the effects of endotoxemia and L-alanyl-L-glutamine (AG) on leucine and protein metabolism were evaluated using a primed constant infusion of [1-14C]leucine, endotoxin, and AG (200 mg/mL) solution or an infusion of [1-14C]leucine without endotoxin or AG. The specificity of the effect of exogenous alanine and glutamine was evaluated by a single infusion of alanine, glutamine, and glycine in a separate study. RESULTS: Endotoxin treatment induced more negative net protein balance caused mainly by an increase in whole-body proteolysis. Protein synthesis increased in kidneys, colon, and spleen, while a decrease was observed in skeletal muscle. The impressive effects of AG were the decrease in plasma branched-chain amino acid (BCAA) levels, decrease in leucine oxidized fraction, and improvement of protein balance associated with a decrease in whole-body proteolysis. Similar changes in leucine and protein metabolism were induced by infusion of alanine or glutamine but not by infusion of glycine. CONCLUSIONS: IV administration of alanine or glutamine improves protein balance and decreases leucine oxidized fraction in postabsorptive state and in endotoxemia. Decreased proteolysis is the main cause of decreased plasma BCAA levels after AG treatment.     

Effect of long-term changes in diet and exercise on plasma leptin concentrations

BACKGROUND: Although it is known that plasma leptin concentrations correlate with the amount of adipose tissue in the body, little information is available on the long-term effects on leptin concentrations of changes in diet and exercise. OBJECTIVE: We wanted to examine whether changes in dietary energy sources and exercise-mediated energy expenditure, alone or in combination, affect plasma leptin concentrations. DESIGN: In a randomized, 2 x 2 factorial trial, 186 men with metabolic syndrome were divided into 4 groups: diet, exercise, a combination of diet and exercise, and control. Data on dietary intake, physical fitness, and demographics were collected and plasma leptin concentrations were measured before and after a 1-y intervention period. RESULTS: Plasma leptin concentrations, body mass index, and fat mass decreased in association with long-term reductions in food intake as well as increased physical activity. By adjusting for either body mass index or fat mass, we observed a highly significant reduction in plasma leptin concentration after both the diet and the exercise interventions. There was no interaction between the interventions, suggesting a direct and additive effect of changes in diet and physical activity on plasma leptin concentrations. CONCLUSION: Long-term changes in lifestyle consisting of decreased intake of dietary fat and increased physical activity reduced plasma leptin concentrations in humans beyond the reduction expected as a result of changes in fat mass.     

Dosing and efficacy of glutamine supplementation in human exercise and sport training

Some athletes can have high intakes of l-glutamine because of their high energy and protein intakes and also because they consume protein supplements, protein hydrolysates, and free amino acids. Prolonged exercise and periods of heavy training are associated with a decrease in the plasma glutamine concentration and this has been suggested to be a potential cause of the exercise-induced immune impairment and increased susceptibility to infection in athletes. However, several recent glutamine feeding intervention studies indicate that although the plasma glutamine concentration can be kept constant during and after prolonged strenuous exercise, the glutamine supplementation does not prevent the postexercise changes in several aspects of immune function. Although glutamine is essential for lymphocyte proliferation, the plasma glutamine concentration does not fall sufficiently low after exercise to compromise the rate of proliferation. Acute intakes of glutamine of approximately 20-30 g seem to be without ill effect in healthy adult humans and no harm was reported in 1 study in which athletes consumed 28 g glutamine every day for 14 d. Doses of up to 0.65 g/kg body mass of glutamine (in solution or as a suspension) have been reported to be tolerated by patients and did not result in abnormal plasma ammonia levels. However, the suggested reasons for taking glutamine supplements (support for immune system, increased glycogen synthesis, anticatabolic effect) have received little support from well-controlled scientific studies in healthy, well-nourished humans.     

Effect of folic acid supplementation on plasma zinc concentrations of young women

OBJECTIVE: Women of reproductive age are advised to consume supplements or fortified foods containing at least 400 microg/d folic acid for the prevention of neural tubes defects. Concerns exist about the adverse effects of folic acid on zinc status. METHODS: Seventy-eight women (18 to 49 y) were assigned for 12-wk to receive either a placebo or a 400 microg/d folic acid supplement. RESULTS: At 12-wk mean (95% CI) red cell folate increased by 431 (350-511) nmol/L in the supplemented group relative to placebo (P < 0.001) but there was no change in plasma zinc in either group (P = 0.213). CONCLUSIONS: Folic acid supplementation does not reduce plasma zinc concentrations in women of childbearing age.     

Effect of intermittent glutamine supplementation on skeletal muscle is not long-lasting in very old rats

Background and objective

Muscle is the major site for glutamine synthesis via glutamine synthetase (GS). This enzyme is increased 1.5–2 fold in 25–27-mo rats and may be a consequence of aging-induced stress. This stimulation is similar to the induction observed following a catabolic state such as glucocorticoid treatment (6 to 24 months). Although oral glutamine supply regulates the plasma glutamine level, nothing is known if this supplementation is interrupted before the experiment.

Design

Adult (8-mo) and very old (27-mo) female rats were exposed to intermittent glutamine supplementation for 50 % of their age lifetime. Treated rats received glutamine added to their drinking water and control rats water alone but the effect of glutamine supplementation was only studied 15 days after the last supplementation.

Results

Glutamine pretreatment discontinued 15 days before the experiment increased plasma glutamine to ～ 0.6 mM, a normal value in very old rats. However, it failed to decrease the up-regulated GS activity in skeletal muscle from very old rats.

Conclusion

Our results suggest that long-term treatment with glutamine started before advanced age but discontinued 15 days before rat sacrifice is effective in increasing plasma glutamine to recover basal adult value and in maintaining plasma glutamine in very old rats, but has no long-lasting effect on the GS activity of skeletal muscle with advanced age.     

丙氨酰-谷氨酰胺二肽对烧伤大鼠血清谷胱甘肽浓度及抗氧化作用的影响

目的：研究丙氨酰－谷氨酰胺二肽（Ala-Gln)对烧伤大鼠血清谷胱甘肽（GSH）浓度及抗氧化作用的影响。方法：SD雄性大鼠30只，行烧伤和中心静脉插管后，随机分为三组，每组10只，A组为对照组，B组为常规TPN组，C组为含Ala-Gln的肠外营养组（Ala-Gln-PN)。7天后测定血清内谷胱甘肽、超氧化物歧化酶（SOD）及血清黄嘌呤氧化酶（XOD）浓度。结果：Ala-Gln组血清中GSH和SOD浓度明显升高，XOD明显减少，与对照组和TPN组比均有显著差异（P＜0．05）。结论：Ala-Gln能降低死亡率，明显升高血液中GSH浓度并能增强抗氧化作用。     

Dose dependency of the effect of ornithine alpha-ketoglutarate on tissue glutamine concentrations and hypercatabolic response in endotoxaemic rats

The optimal dosage of ornithine alpha-ketoglutarate (OKG) for repleting tissue glutamine (Gln) concentrations and maintaining N homeostasis after injury is unknown. We set out to perform 'dose-ranging' of OKG supplementation after an endotoxaemic challenge. Sixty-one male Wistar rats were injected with 3 mg lipopolysaccharide (LPS) from Escherichia coli/kg (n 50) or saline vehicle (9 g NaCl/l; controls n 11). After a 24 h fast, survivors were fed by gavage for 48 h with a polymeric standard diet (879 kJ/kg per d and 1.18 g N/kg per d) supplemented with non-essential amino acids (control, n 11; LPS-OKG-0.0, n 9), or with 0.5 g OKG/kg per d (LPS-OKG-0.5, n 12), 1.5 OKG/kg per d (LPS-OKG-1.5, n 11) or 4.5 g OKG/kg per d (LPS-OKG-4.5, n 10). The diets for all groups were made isonitrogenous with the LPS-OKG-4.5 diet by adding an appropriate amount of non-essential amino acids. Rats were killed on day 3 for blood and tissue sampling (muscle, jejunum mucosa, liver). Urine was collected daily for 3-methylhistidine and total N assays. The OKG dose was correlated with Gln concentrations in every tissue and with cumulative N balance (Spearman test, P<0.01). 3-Methylhistidine excretion was increased in endotoxaemic groups compared with controls (ANOVA, P<0.05) except in the LPS-OKG-4.5 group. Only the LPS-OKG-4.5 group achieved a positive post-injury N balance (t test, P<0.05). In conclusion, OKG exerted a dose-dependent effect on tissue Gln concentration and N balance, but only the highest dosage counteracted myofibrillar hypercatabolism and caused a positive N balance.     

丙氨酰胺谷氨酰胺对烫伤大鼠的作用

目的研究添加丙氨酰谷氨酰胺(Ala-Gln)全胃肠外营养对烫伤大鼠的蛋白质代谢、肠粘膜形态学、创面肉芽组织的影响。方法将22只30%TBSAⅢ度烫伤SD大鼠行颈外静脉插管后,随机分为传统TPN组(传统组)和添加二肽TPN组(二伏组),每组各11例,两组接受等热量(780kg     

Immunosuppression in undernourished rats: the effect of glutamine supplementation

OBJECTIVE: The aim of our study is to determine the effect of a 30-day-period caloric restriction (CR) upon the immune response of rats and the influence of glutamine upon mononuclear cells proliferation and cytokine production.METHODS: Male albino Wistar rats were submitted to CR receiving an amount of food equivalent to 50% of the mean amount consumed by the control animals. We measured the incorporation of [2-14C]-thymidine by lymphocytes obtained from the spleen and mesenteric lymph nodes, plasma glucose and glutamine concentration, as well as cytokine production by cultivated cells, in the presence of glutamine.RESULTS: Rats submitted to CR presented reduced body weight (49%) and decreased splenic leukocyte number. CR led to a reduction in the proliferative response of lymphocyte. Spleenocytes from CR animals produced less gamma-interferon and interleukins 1, 4 and 10 in 48 h culture than did those from control rats. The same pattern is observed in cells obtained from the mesenteric lymph nodes. The addition of glutamine 2mM to the culture medium restored spleen and mesenteric lymph node cells' proliferative response and the production of interleukin 2 by cells obtained from the spleen and from the mesenteric lymph nodes.CONCLUSIONS: The present data reinforce that undernutrition decreases in vitro immune cell function and indicates that, in such circumstances, glutamine supplementation could reverse some of the changes observed in the functionality of cultured immune cells. The presence of the amino acid at physiological concentration, however, reinforces the diversion of the immune response towards a Th(1)-like response.