Inhibition of mitogen-activated proliferation of human lymphocytes in vitro by high concentrations of glutamine

ABSTRACT

We invetigated the influence of hogh concentrations of glutamine and aspargine on in vitro cellular growth of lymphocytes stimulated with phytohaemaglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM), a recognized test of cellular immunocompetence. Human peripheral lymphocytes were cultured in flat-bottomed 96-well microplates at 37§ C for 96 (PHA and Con A) or 144 hours (PWM) in the presence of a mitogen at different concentrations and either glutamine or asparagine supplemented at doses of 2, 4 or 8 mM. Lymphocyte reactivity, meas ured by the incorporation of tritiated thymidine into cellular DNA, was compared to identical cultures in the absence of supplemented amino acids (controls). We found that glutamine in doses of 2 mM and higher inhibited lymphocyte proliferation of mitogen-stimulated human lymphocyes, whereas asparagine caused no effect. These results demonstrate that, although necessary for cellular division in moderate amounts, glutamine in high concentrations has the reverse effect