Arginine-supplemented diets improve survival in gut-derived sepsis and peritonitis by modulating bacterial clearance: The role of nitric oxide

Objective: The effect of arginine on survival rates and host defense mechanisms was studied using two clinically relevant models of infection that included transfusion-induced immunosuppression. Summary Background Data: Dietary arginine will improve resistance to infection but its role in transfusion-induced immunosuppression and bacterial translocation (gut derived sepsis) has not been defined. Methods: Balb/c mice were fed for 10 days with either a defined AIN-76A diet, an AIN-76A diet supplemented with 2% arginine, an AIN-76A diet supplemented with 4% glycine, or standard laboratory chow. In most experiments, the mice were then transfused with allogeneic blood and allowed to feed for an additional 5 days before undergoing either cecal ligation and puncture (CLP) or gavage with 10¹⁰ Escherichia coli and a 20% burn injury. Additional animals fed with the arginine supplemented diet were treated with the nitric oxide inhibitor Nω- Nitro L-arginine (NNA) before gavage and burn. The effect of these diets and NNA on the degree of translocation of ¹⁴C-radiolabeled E. coli from the intestine and the ability of the host to kill translocated organisms was also investigated. Mice were fed and received transfusion, gavage, and burn as above. Mesenteric lymph nodes (MLN), liver and spleen were harvested 4 hours postburn. Results: Survival after CLP was 56% in the arginine-supplemented group versus 28% in the AIN 76A group and 20% in the chow group (p < 0.02). After gavage and burn, survival was 100% in the arginine supplemented group versus 50% in both the glycine-supplemented and chow groups and 35% in the AIN-76A group (p < 0.01). In animals receiving the arginine-supplemented diet, treatment with NNA decreased survival from 95% to 30.5% (p < 0.0001). Greater translocation, as measured by radionuclide counts, was observed to the MLN of the AIN-76A group. However, there was no difference in translocation to the liver and spleen related to dietary group. Quantitative colony counts and the calculated percentage of remaining viable bacteria showed that the ability to kill translocated organisms was significantly enhanced in animals receiving arginine. Treatment with NNA reversed the beneficial effects of arginine on immune defense. Conclusions: The benefit of arginine appears to be mediated by improved bactericidal mechanisms via the arginine-nitric oxide pathway.