DIETARY ARGININE AND GLUTAMINE COMBINATION IMPROVES SURVIVAL IN SEPTIC MICE

The individual nutrients arginine and glutamine modulate the host resistance against infection, but prospective trials have not demonstrated their combined effects in septic mice. The following studies was undertaken to determine whether dietary supplementation with arginine and glutamine can be used to up-regulate the host resistance following challenge with methicillin-resistant Staphylococcus aureus (MRSA) organisms in mice. Sixty BALB/c mice were randomized into 4 groups. Group A mice were fed 20% casein diet (control), whereas the mice in Groups B, C, and D were maintained on 20% casein diet supplemented with 2% arginine, 4% glutamine, and 2% arginine plus 4% glutamine, respectively. The diets were isocaloric and isonitrogenous. On the 10th day on these diets, each mouse was challenged with 2.0x10(8) colony forming units (CFU) of MRSA organisms intravenously and mortality was noted for 20 days. The survival rate in Group A (20%) was significantly lower compared to the rates in Groups B (60%), C (66%), and D (80%) (p < 0.05). The survival rate in Group D tended to be higher than that in Groups B and C, but this was not statistically different (p>0.05). Of the surviving mice 20 days after infection, in Group D, 11 out of 12 (92%) eliminated the organisms in comparison with 0 out of 3 (0%), 6 out of 9 (66%), 6 out of 10 (60%) in Groups A, B, and C, respectively. Furthermore, the splenic weight in Group D (190 +/- 50mg) tended to be heavier than that in Groups B (160 +/- 30mg) and C (150 +/- 20mg), but without significant difference (p > 0.05). Although there was a trend toward signifcance, there was no statistical difference between the single amino acids and the combined amino acids in survival and CFU recovery of MRSA organisms from the organs. However, taken into consideration the higher survival rate, the profound reduction of MRSA organisms, and the heavier splenic weight, the present results suggest that combined therapy with dietary arginine and glutamine may to be used to an advantage to enhance the host defense following induction of sepsis and may play an important role as a nutritional immunomodulator in critically ill or septic patients.