The effects of an arginine-free enteral diet on wound healing and immune function in the postsurgical rat

Critically ill patients have increased rates of sepsis partly due to a down-regulated immune system. Nutrients may modulate the immune system. The following studies were performed to determine whether arginine is one of these “essential” nutrients for the immune system. Thirty-two male Spraque-Dawley rats (weighing 175 g) were divided into two groups that were pair-fed with either an elemental, arginine-supplemented enteral diet, or the same diet with arginine removed and replaced with glycine. Both diets were isocaloric, isoosmolar, and isonitrogenous. After 6 days on the diet, animals underwent testing. There were no significant differences between the arginine-supplemented and the arginine-free diet groups in blood glucose or hematocrit. The arginine-supplemented animals had higher serum albumin (4.1 ± 0.1 mg/dL v 3.6 ± 0.1 mg/dL; P = .035) and serum protein levels (5.2 ± 0.1 mg/dL v 4.3 ± 0.1 mg/dL; P = .041); and had higher thymus gland (0.53 ± 0.03 g v 0.44 ± 0.02 g; P < .0001) and spleen weights (0.66 ± 0.01 g v 0.57 ± 0.01 g; P < .01). Daily total urinary nitrogen excretion, nitrogen balance, and weight gain showed a tendency for the arginine-supplemented animals to retain more of their nitrogen calories. There was no difference in the amount of hydroxyproline (OHP) found in the wound cylinders of either group (both 25.6 μg OHP/cm polytetrafluoroethylene) but the arginine-supplemented group's wounds had greater wound bursting strengths (429 ± 3 g/cm v 350 ± 7 g/cm; P = .044). Lymphocyte mitogenic activation was higher in arginine-supplemented animals than in arginine-free animals (phytohemagglutinin stimulation index: 28.4 ± 1.2 v 21.2 ± 1.0, P = .043; Concalavilin A: 56.9 ± 2.8 v 38.8 ± 1.3, P = .025). Bacterial killing by peritoneal macrophages from arginine-free animals was decreased compared with arginine-supplemented animals (NS at 0 and 60 minutes, but 30% v 121% of time-0 bacterial inoculum at 120 minutes; P = .0004). The macrophage chemotactic index was lower in arginine-free animals than in arginine-supplemented animals (1.6 ± 0.04 v 2.1 ± 0.03; P < .05). This study shows that animals fed arginine-supplemented diets had longer survival to bacterial challenge and improved immune parameters. In addition, they had better wound healing and protein levels were higher. Arginine may be a conditionally essential nutrient for stressed and critically ill patients.