GLUTAMINE ENHANCES IMMUNOREGULATION OF TUMOR-GROWTH

Background: It is known that tumor progression is associated with a depletion in host glutamine (Gln) stores and a depression of natural killer (NK) cell activity. After demonstrating an in vitro dependence of NK cell activity on Gln and glutathione concentration, this study evaluated the effects of oral Gln on Gln and glutathione metabolism, NK cell activity, and tumor growth in the tumor-bearing rat. Methods: Two days before tumor implantation, rats (n = 32) were randomized to receive Gln (1 g/kg/d) or an isonitrogenous amount of glycine by gavage and pair-fed food. On day 21 after tumor implantation, rats were killed, and tumors were measured and processed for glutaminase activity, glutathione content, and tumor morphometrics. Splenic lymphocytes were assayed for NK cell activity via a chromium (Cr-51) release assay using YAC (NK-cell-sensitive mouse tumor cell line) target cells. Blood Gln and glutathione were measured. A second set of rats (n = 16) were treated similarly except that ketamine was given twice weekly to suppress NK cell activity. Results: During the 3-week study period, tumor growth was decreased by 40% in the Gln group. This decrease in growth was associated with a 30% increase in NK cell activity. Administration of ketamine to rats completely reversed the higher NK cell activity and decreased the tumor growth seen in the Gln-treated group. Conclusions: These data indicate that oral Gln supplementation, through support of host Gln stores and glutathione production, may decrease tumor growth by enhancing NK cell activity.