The amino acid arginine has anabolic and immunostimulatory properties. This study evaluated the potency of arginine in limiting the severe nutritional and immunological insults of protein calorie malnutrition and increasing tumor load. In protein-depleted A/J mice (n = 340) bearing either an immunogenic (C1300) or poorly immunogenic (TBJ) neuroblastoma, arginine supplementation [1%] significantly augmented T lymphocyte responses (mitogenesis, interleukin-2 production) compared with both a glycine-supplemented and nonsupplemented group. Arginine supplementation significantly retarded the growth of C1300 and prolonged median host survival. These results correlated with augmented autologous mixed lymphocyte tumor cell responses and enhanced specific cytotoxicity. This anti-tumor effect was not demonstrated in mice bearing TBJ where both arginine and glycine stimulated tumor growth compared with nonsupplemented mice. There was no significant difference between arginine and glycine in preservation of carcass weight. These studies suggest that the immunostimulatory effects of arginine are not due to supplemental nitrogen and that an associated antitumor effect is dependent on tumor antigenicity.
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