Amino acid nutrition and immune function in tumour-bearing rats: a comparison of glutamine-, arginine- and ornithine 2-oxoglutarate-supplemented diets

Dietary supplementation with glutamine (Gln), arginine (Arg) or ornithine 2 -oxoglutarate (alpha-ketoglutarate; OKG) has attracted recent attention for the potential to im prove anti-cancer immune function. However, since thes e compounds have not been compared systematically in an internally controll ed study, their relative efficacy is difficult to estimate. Buffalo rats we re fed on nutritionally complete semi-purified diets supplemented with Gln, Arg or OKG for 14 days after implantation of the Morris hepatoma 7777 (n g reater than or equal to 7 per diet). The control diet was made isonitrogeno us and isoenergetic by addition of a mixture of non-essential amino acids. After 14 days, peritoneal macrophages and splenocytes were isolated to dete rmine cell phenotypes, macrophage cytostatic activity and natural killer (N K) cell cytotoxicity, as well as nitric oxide (NO) and cytokine production. Diet had no effect on tumour weight (1.6+/-0.2 g; n = 59). However, rats f ed OKG had increased macrophage cytostatic activity and NK cell cytotoxicit y (P < 0.05). Although enhanced killing ability by NK cells was associated with higher splenocyte NO production (P < 0.04), increased cytotoxicity was not inhibited by a specific inhibitor of inducible NO synthase. The propor tion of interleukin-2-receptor-positive T cells after stimulation increased in rats fed OKG (P < 0.05); however, cytokine production was not affected by diet. None of OKG, Gln or Arg altered tumour growth compared with a cont rol mixture of non-essential amino acids. These results suggest no net adva ntage for anti-cancer immunity, but do not preclude benefits in immune resp onses to disease recurrence or metastasis, therapy or secondary infection.