GLUTAMINE ENHANCES IMMUNOREGULATION OF TUMOR-GROWTH

Background: It is known that tumor progression is associated with a de pletion in host glutamine (Gln) stores and a depression of natural kil ler (NK) cell activity. After demonstrating an in vitro dependence of NK cell activity on Gln and glutathione concentration, this study eval uated the effects of oral Gln on Gln and glutathione metabolism, NK ce ll activity, and tumor growth in the tumor-bearing rat. Methods: Two d ays before tumor implantation, rats (n = 32) were randomized to receiv e 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, a nd tumors were measured and processed for glutaminase activity, glutat hione content, and tumor morphometrics. Splenic lymphocytes were assay ed 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 w as decreased by 40% in the Gln group. This decrease in growth was asso ciated with a 30% increase in NK cell activity. Administration of keta mine to rats completely reversed the higher NK cell activity and decre ased the tumor growth seen in the Gln-treated group. Conclusions: Thes e data indicate that oral Gln supplementation, through support of host Gln stores and glutathione production, may decrease tumor growth by e nhancing NK cell activity.