Effects of diazepam on neutrophil (PMN) free amino acid profiles and immune functions in vitro. Metabolical and immunological consequences of L-alanyl-L-glutamine supplementation

The objective of this study was to determine the effects of diazepam, L-ala nyl-L-glutamine (ala-gln) or diazepam combined with ala-gln on polymorphonu clear leukocyte (PMN) free amino acid profiles. In a parallel study the eff ects on PMN immune functions were also documented for the first time. The i ncubation of whole blood with diazepam led to significant changes in PMN fr ee glutamine, aspartate, glutamate, ornithine, arginine, citrulline, taurin e and methionine as well as branched chain and neutral amino acid concentra tions. Ala-gln caused significant increases in PMN glutamine and alanine an d asparagine, aspartate, glutamate, ornithine, arginine, serine and glycine profiles. Regarding PMN immune functions, diazepam significantly decreased superoxide anion (O-2(-)) and hydrogen peroxide production (H2O2) and myel operoxidase activity (MPO) while ala-gln significantly increased PMN immune functions. Ala-gln supplemented to diazepam largely reversed the changes i n PMN amino acid profiles and PMN immune functions brought about by diazepa m. Overall, diazepam or ale-gin lead to significant changes in PMN free ami no acids. Important PMN immune functions also seem to be affected. In regar ds to the results, there is significant relevance to the pharmacological re gimens which enhance the supply of diazepam or ala-gln in whole blood sugge sting that considerable changes in PMN "labile free amino acid pool" occur. These regimens often follow beneficial nutritional therapy or maleficent p harmacological stress and may be one of the determinants in cell nutrition which influence PMN function. It is partially through its effect on PMN lab ile free amino acid pool that ala-gln supplemented to diazepam may maintain PMN immune functions in vitro. (C) 2001 Elsevier Science Inc. All rights r eserved.