THE INFLUENCE OF ORGANIC-ACIDS ON THE PROLIFERATION OF HUMAN PERIPHERAL LYMPHOCYTES ACTIVATED BY CONCANAVALIN-A AND POKEWEED MITOGEN

The present study was undertaken to assess the influence of 25 organic acids, which appear in high concentrations in tissues of patients wit h various organic acidaemias, on the proliferation of human peripheral lymphocytes stimulated with concanavalin A (Con A) (a T-cell activato r) and pokeweed mitogen (PWM) (predominantly a B-cell activator). Mono nuclear cells were cultivated in flat-bottomed 96-well microplates at 37 degrees C for 96 (Con A) or 144 h (PWM) in the presence of one mito gen at different concentrations and of one acid at doses ranging from 1 to 5 mM. Control cultures did not contain any acid. Cell reactivity was measured by the incorporation of tritiated thymidine into cellular DNA. We observed that, among the 25 acids tested, aminoadipic (AAD), 2-hydroxy-3-methylvaleric (HMV), 2-ketoisocaproic (KIC), 2-methylbutyr ic (MBA), propionic (PPA) and tiglic (TIG) acids strongly suppressed l ymphocyte DNA synthesis in Con A-supplemented cultures, whereas in cul tures stimulated with PWM, 2-ketoisovaleric (KIV) and PPA acids presen ted the same effect. In contrast, lactic (LAC) and pyruvic (PYR) acids activated lymphocyte DNA synthesis in cultures treated with Con A, th e same effect occurring with LAC acid for PWM-stimulated lymphocytes. The most inhibitory or stimulatory acids were added to cultures at dif ferent times after the beginning of the incubation period when mitogen s were added. Except for HMV, KIC, PPA and LAC acids, whose actions pe rsisted even after 24 h from the beginning of culture, the others only exerted their effects when added at time zero. The present study ther efore demonstrated that some organic acids modulate DNA synthesis in C on A- and PWM-stimulated human lymphocytes. (C) 1997 International Soc iety for Immunopharmacology.