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 with various organic acidaemias, on the proliferation of human peripheral lymphocytes stimulated with concanavalin A (Con A) (a T-cell activator) and pokeweed mitogen (PWM) (predominantly a B-cell activator). Mononuclear 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 mitogen 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-methylbutyric (MBA), propionic (PPA) and tiglic (TIG) acids strongly suppressed lymphocyte DNA synthesis in Con A-supplemented cultures, whereas in cultures stimulated with PWM, 2-ketoisovaleric (KIV) and PPA acids presented the same effect. In contrast, lactic (LAC) and pyruvic (PYR) acids activated lymphocyte DNA synthesis in cultures treated with Con A, the same effect occurring with LAC acid for PWM-stimulated lymphocytes. The most inhibitory or stimulatory acids were added to cultures at different times after the beginning of the incubation period when mitogens were added. Except for HMV, KIC, PPA and LAC acids, whose actions persisted even after 24 h from the beginning of culture, the others only exerted their effects when added at time zero. The present study therefore demonstrated that some organic acids modulate DNA synthesis in Con A- and PWM-stimulated human lymphocytes.