Jones B M, Bird M, Massey P, Millar D, Miller J J, Reeves S, Salaman J R
Br Med J. 1977 Sep 24;2(6090):792-5. doi: 10.1136/bmj.2.6090.792.
Niridazole, an antischistosomal agent, was given to renal transplant recipients in addition to azathioprine and prednisolone, as there is experimental evidence that this combination of drugs is highly immunosuppressive. Sera obtained from kidney-graft recipients during the first two weeks after transplantation were examined for their ability to inhibit the one-way mixed lymphocyte reaction (MLR). Sera from seven patients receiving azathioprine, prednisolone, and niridazole (triple-drug treatment), five patients receiving azathioprine and prednisolone, and two other patients treated with niridazole alone for schistosomiasis produced MLR inhibition by comparison with pretreatment (control) sera.A mean of 78% inhibition was observed with sera taken after one day's treatment with the three-drug combination, whereas this level of in-vitro immunosuppression occurred only after eight days of treatment with azathioprine and prednisolone. Niridazole alone produced an effect similar to azathioprine and prednisolone. Concentrated dialysate of urine from a patient receiving triple-drug treatment not only inhibited the MLR but also significantly prolonged the survival of heterotopic heart allografts in rats, whereas dialysate from the same patient after niridazole had been stopped gave less MLR inhibition and failed to prolong heart allograft survival.Since niridazole thus increased the in-vitro and in-vivo immunosuppressive action of azathioprine and prednisolone, we suggest that this triple-drug combination might be useful for preventing early acute kidney graft rejection.
硝咪唑是一种抗血吸虫药，除了硫唑嘌呤和泼尼松龙外，还将其给予肾移植受者，因为有实验证据表明这种药物组合具有高度免疫抑制作用。对肾移植受者在移植后头两周内采集的血清进行检测，以评估其抑制单向混合淋巴细胞反应（MLR）的能力。与预处理（对照）血清相比，接受硫唑嘌呤、泼尼松龙和硝咪唑（三联药物治疗）的7名患者、接受硫唑嘌呤和泼尼松龙的5名患者以及另外2名单独接受硝咪唑治疗血吸虫病的患者的血清产生了MLR抑制作用。三联药物组合治疗一天后采集的血清平均抑制率为78%，而硫唑嘌呤和泼尼松龙治疗八天后才出现这种体外免疫抑制水平。单独使用硝咪唑产生的效果与硫唑嘌呤和泼尼松龙相似。接受三联药物治疗患者的浓缩尿液透析液不仅抑制了MLR，还显著延长了大鼠异位心脏同种异体移植的存活时间，而停止使用硝咪唑后同一患者的透析液对MLR的抑制作用较小，且未能延长心脏同种异体移植的存活时间。由于硝咪唑因此增强了硫唑嘌呤和泼尼松龙的体外和体内免疫抑制作用，我们认为这种三联药物组合可能有助于预防早期急性肾移植排斥反应。
