Lucas S V, Daniels J C, Schubert R D, Simpson J M, Mahmoud A A, warren K S, David J R, Webster L T
J Immunol. 1977 Feb;118(2):418-22.
Administration of the antischistosomal compound niridazole to mice, guinea pigs, and humans results in the suppression of several manifestations of cell-mediated immunity. Sera from animals treated with niridazole blocked the in vitro production of migration inhibitory factor (MIF) while niridazole itself was inactive, suggesting that these effects are caused by water soluble mediators. We now report that crude extracts prepared from the urine of rats and a patient receiving nirdazole, but not from pretreatment control urine, similarly suppress antigen-induced inhibition of migration of peritoneal exudate cells from sensitized guinea pigs. With immunosuppressive activity monitored by the direct MIF assay, combined solvent extraction and chromatographic techniques were used to fractionate immunosuppressive activity from the urine of niridazole-treated rats and the patient; the most active fractions, purified about 100-to 1000-fold as compared to methanol-water extracts of dried voided urine, inhibited MIF production at 0.1 to 0.01 ng/ml of assay mixture. These purified fractions also showed immunosuppressive activity by an in vivo assay wherein doses as low as 1 mug/kg injected intravenously (i.v.) into mice suppressed cell-mediated granuloma formation around Schistosoma manisoni eggs. Identically purified fractions prepared from urine of rats and the patient before they received niridazole showed no immunosuppressive activity either in the MIF or in the granuloma assay systems.
给小鼠、豚鼠和人类施用抗血吸虫化合物硝唑咪会导致细胞介导免疫的几种表现受到抑制。用硝唑咪处理的动物血清可阻断体外迁移抑制因子（MIF）的产生，而硝唑咪本身无活性，这表明这些作用是由水溶性介质引起的。我们现在报告，从接受硝唑咪治疗的大鼠和患者尿液中制备的粗提物，但未从预处理对照尿液中制备的粗提物，同样能抑制抗原诱导的致敏豚鼠腹腔渗出细胞迁移的抑制作用。通过直接MIF测定监测免疫抑制活性，采用联合溶剂萃取和色谱技术从硝唑咪处理的大鼠和患者尿液中分离免疫抑制活性；与干燥排尿尿液的甲醇 - 水提取物相比，活性最高的馏分纯化了约100至1000倍，在测定混合物浓度为0.1至0.01 ng/ml时抑制MIF产生。这些纯化的馏分在体内试验中也显示出免疫抑制活性，其中静脉内（i.v.）注射到小鼠体内低至1μg/kg的剂量可抑制曼氏血吸虫卵周围细胞介导的肉芽肿形成。从大鼠和患者接受硝唑咪治疗之前的尿液中制备的相同纯化馏分在MIF或肉芽肿测定系统中均未显示出免疫抑制活性。
