Effect of dietary glutamate on chemotherapy-induced immunosuppression

Chemotherapy causes severe host immune depression and consequently increase s susceptibility to infection. Dietary glutamate (GLU) serves as a stable s ubstrate for the formation of glutamine (GLN), which is an important fuel a nd 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 r eceived a single intraperitoneal injection of methotrexate (MTX, 20 mg/kg B W). Two in vivo immune tests, delayed-type hypersensitivity (DTH) and popli teal lymphoproliferation (PLP), were performed 3 and 7 d after MTX treatmen t. Food intake and body weight decreased significantly immediately after MT X treatment and gradually recovered after 8 d with no significant differenc e among treatment groups. In a 23-d feeding study, no significant differenc e was found in the DTH response, but the PLP response increased in a GLU do se related fashion (83 and 133% increases for the 4 and 8% GLU diets, respe ctively). In a 44-d feeding study, the DTH response increased 61 and 83%, w hile the PLP response increased 191 and 382% for the 4 and 8% GLU diets, re spectively. Plasma GLN, GLU, or glutathione (GSH) levels were increased by dietary GLU, but only in the immediate postprandial state. In summary, diet ary GLU improves immune status of rats recovering from MTX treatment. The i mmune-enhancing effect of dietary GLU was dose-dependent and more pronounce d after a longer duration of dietary GLU intake. (C) Elsevier Science Inc. 1999.