The high rate of glutamine utilization by neutrophils, macrophages and lymphocytes and its increase when these cells are challenged suggests that provision of glutamine might be important to the function of these cells and so to the ability to mount an efficient immune response. Over 30 years ago, it was reported that the addition of asparaginase or glutaminase to cultures of lymphocytes prevented the cells from proliferating (Hirsch, 1970; Simberkoff and Thomas, 1970). Furthermore, asparaginase treatment of animals leads to immunosuppression (Brambilla et al., 1970; Chakrabaty and Friedman, 1970; Ashworth and MacLennan, 1974; Kafkewitz and Bendich, 1983). The immunosuppressive effect of asparaginase was shown to be due to its ability to hydrolyse glutamine and so decrease its availability to the immune system (Ashworth and MacLennan, 1974; Durden and Distasio, 1981; Kafkewitz and Bendich, 1983). These observations suggest that a supply of glutamine is required for the immune system to function optimally. A number of specific immunomodulatory actions of glutamine have now been reported.

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