Immunomodulatory mechanisms of arginine

Dietary supplementation with the amino acid arginine augments T-lymphocyte activation in response to mitogens in clinical and experimental studies. In experimental models arginine enhances specific T cell antitumor immunity. The mechanism of these immunostimulatory effects of arginine on T cell function is unclear, and the scope and specificity of arginine's influence on other components of the effector immune response such as natural killer (NK) cells and macrophages are unknown. To evaluate the role of arginine in these responses, CBA/J mice (n = 100) were randomized to receive either 1% arginine supplementation or isonitrogenous (1.7%) glycine supplementation for at least 10 days. There was no significant differences in mean body weight between groups during feeding. Arginine supplementation significantly (p less than 0.05) enhanced cytotoxic T-lymphocyte development, poly IC-inducible NK activity, and the kinetics of interleukin-2 receptor expression on activated T cells. Basal- and endotoxin-induced macrophage interleukin-1 and superoxide production were not significantly influenced by supplemental arginine although macrophage cytotoxicity in response to gamma-interferon was augmented (p = 0.07). In subsequent in vitro studies we established that certain effects (NK, cytotoxic T-lymphocyte, and T cell activation) were reproducible after preincubation for 72 hours in pharmacologic levels of arginine. The data strongly suggest that arginine mediates a direct effect on components of the immune system, which results in enhanced production or use of lymphokines.