Effect of dietary glutamate on chemotherapy-induced immunosuppression

Chemotherapy causes severe host immune depression and consequently increases susceptibility to infection. Dietary glutamate (GLU) serves as a stable substrate for the formation of glutamine (GLN), which is an important fuel and metabolic precursor for the immune cells. The effect of addition of GLU to a GLN/GLU-free amino acid diet upon immune response was studied in rats recovering from chemotherapy. Animals were fed a 0, 4, or 8% GLU diet and received a single intraperitoneal injection of methotrexate (MTX, 20 mg/kg BW). Two in vivo immune tests, delayed-type hypersensitivity (DTH) and popliteal lymphoproliferation (PLP), were performed 3 and 7 d after MTX treatment. Food intake and body weight decreased significantly immediately after MTX treatment and gradually recovered after 8 d with no significant difference among treatment groups. In a 23-d feeding study, no significant difference was found in the DTH response, but the PLP response increased in a GLU dose related fashion (83 and 133% increases for the 4 and 8% GLU diets, respectively). In a 44-d feeding study, the DTH response increased 61 and 83%, while the PLP response increased 191 and 382% for the 4 and 8% GLU diets, respectively. Plasma GLN, GLU, or glutathione (GSH) levels were increased by dietary GLU, but only in the immediate postprandial state. In summary, dietary GLU improves immune status of rats recovering from MTX treatment. The immune-enhancing effect of dietary GLU was dose-dependent and more pronounced after a longer duration of dietary GLU intake.