Metcalf J F, Wilson G B
J Environ Pathol Toxicol Oncol. 1987 Mar-Apr;7(4):27-37.
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.
在阿米卡星长期临床使用过程中淋巴细胞反应性抑制的出现促使了相关研究，以评估氨基糖苷类药物和其他抗生素对淋巴细胞反应性的影响。测定了三种常用氨基糖苷类药物（庆大霉素、卡那霉素和阿米卡星）、四环素和青霉素对受植物血凝素（PHA）、刀豆蛋白A（ConA）和商陆有丝分裂原（PWM）刺激的淋巴细胞（DNA合成）的影响。以亚最佳、最佳和超最佳浓度添加有丝分裂原。有丝分裂原与药物同时添加，或在用药物预培养细胞96小时后添加。药物浓度在治疗范围内。在用抗生素预孵育的细胞培养物中，观察到所有氨基糖苷类药物在ConA刺激后均抑制淋巴细胞DNA合成。相比之下，苄青霉素对淋巴细胞转化没有影响。在所有预孵育培养物中，四环素往往会导致对有丝分裂原反应性的抑制。有丝分裂原诱导的淋巴细胞转化对氨基糖苷类药物的敏感性在不同供体之间有所不同。氨基糖苷类药物似乎选择性地抑制或抑制抑制性免疫细胞，特别是在使用亚最佳浓度有丝分裂原时。
