GLUTAMINE - EFFECTS ON THE IMMUNE-SYSTEM, PROTEIN-METABOLISM AND INTESTINAL FUNCTION

Glutamine is the most abundant free amino acid of the human body. In c atabolic stress situations I;uch as after operations, trauma and durin g sepsis the enhanced transport of glutamine to splanchnic organs and to blood cells results in an intracellular depletion of glutamine in s keletal muscle. Glutamine is an important metabolic substrate for cell s cultivated under in vitro conditions and is a precursor for purines, pyrimidines and phospholipids. Increasing evidence suggests that glut amine is a crucial substrate for immunocompetent cells. Glutamine depl etion in the cultivation medium decreases the mitogen-inducible prolif eration of lymphocytes, possibly by arresting the cells in the G(0)-G( 1) phase of the cell cycle. Glutamine depletion in lymphocytes prevent s the formation of signals necessary for late activation. In monocytes glutamine deprivation downregulates surface antigens responsible for antigen preservation and phagocytosis. Glutamine is a precursor for th e synthesis of glutathionine and stimulates the formation of hear-shoc k proteins. Moreover, there are suggestions that glutamine plays a cru cial role in osmotic regulation of cell volume and causes phosphorylat ion of proteins, both of which may stimulate intracellular protein syn thesis. Experimental studies revealed that glutamine deficiency causes a necrotising enterocolitis and increases the mortality of animals su bjected to bacterial stress. First clinical studies have demonstrated a decrease in the incidence of infections and a shortening of the hosp ital stay in patients after bone marrow transplantation by supplementa tion with glutamine. In critically ill patients parenteral glutamine r educed nitrogen loss and caused a reduction of the mortality rate. In surgical patients glutamine evoked an improvement of several immunolog ical parameters. Moreover, glutamine exerted a trophic effect on the i ntestinal mucosa, decreased the intestinal permeability and thus may p revent the translocation of bacteria. In conclusion, glutamine is an i mportant metabolic substrate of rapidly proliferating cells, influence s the cellular hydration state and has multiple effects on the immune system, on intestinal function and on protein metabolism. In several d isease states, glutamine may consequently, become an indispensable nut rient, which should be provided exogenously during artificial nutritio n.