Use of mitogen-induced lymphocyte transformation to assess toxicity of aminoglycosides

The development of suppression of lymphocyte responsiveness during extended clinical use of amikacin promoted studies to evaluate the effects of aminoglycosides and other antibiotics on lymphocyte reactivity. The effects of three commonly used aminoglycosides (gentamicin, kanamycin and amikacin), tetracycline and penicillin on lymphocyte (DNA synthesis) in response to stimulation with phytohemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PWM) were measured. Mitogens were added at suboptimal, optimal and supraoptimal concentrations. The mitogen was added either concomitantly with the drug or 96 hours after preculturing the cells with the drug. Drug concentrations were within therapeutic range. Suppression of lymphocyte DNA synthesis after stimulation with ConA was observed for all the aminoglycosides in cell cultures preincubated with antibiotic. In contrast benzylpenicillin had no effect on lymphocyte transformation. Tetracycline tended to cause suppression of responsiveness to mitogen in all preincubated cultures. Sensitivity of mitogen-induced lymphocyte transformation to aminoglycosides varied between donors. Aminoglycosides appear to selectively suppress or inhibit suppressor immunocytes, particularly when suboptimal concentrations of mitogen are used.