Florentin I, Taylor E, Davigny M, Mathé G, Hadden J W
Int J Immunopharmacol. 1982;4(3):225-33. doi: 10.1016/0192-0561(82)90052-2.
NPT 15392 [9-erythro-(2-hydroxy,3-nonyl)-hypoxanthine] was administered in a single intraperitoneal injection to Balb/c mice at a dose of 0.1 mg/kg. Modifications of immune parameters were evaluated 1-14 days after the treatment. NPT 15392 potentiated antibody responses to both T-dependent (SRBC, TNP-KLH) and T-independent (TNP-LPS) antigens and delayed-type hypersensitivity to oxazolone. The proliferative response of spleen cells from NPT-treated mice to stimulation with PHA was depressed, but that to dextran sulphate was augmented. The responses to Con A or LPS were inconsistently modified. NPT 15392 augmented killer cell functions, including both T cell-mediated cytotoxicity against allogeneic tumor cells and NK cell activity against YAC-1 tumor cells. It slightly augmented or depressed ADCC activity against antibody-coated chicken erythrocytes (CRBC) depending on the time of its administration. Concerning the stimulation of NK cell activity, the effect was more marked on spleen effector cells when NPT 15392 was given i.v. and on peritoneal effector cells when it was given i.p. From these results, T helper cells, B cells, and NK cells appeared to be target cells of NPT 15392 action. The various stimulatory effects peaked at different times according to the immune function tested. In addition, the prolonged, sometimes double-peaked action (antibody response to T-dependent antigens, NK activity) indicates complex mechanisms of action which may involve indirect interactions mediated by lymphokines or monokines.
将NPT 15392[9-赤型-(2-羟基,3-壬基)-次黄嘌呤]以0.1毫克/千克的剂量腹腔注射给Balb/c小鼠。在治疗后1至14天评估免疫参数的变化。NPT 15392增强了对T细胞依赖性抗原(绵羊红细胞、三硝基苯-钥孔戚血蓝蛋白)和T细胞非依赖性抗原(三硝基苯-脂多糖)的抗体反应,以及对恶唑酮的迟发型超敏反应。用NPT处理的小鼠脾脏细胞对PHA刺激的增殖反应受到抑制,但对硫酸葡聚糖的增殖反应增强。对刀豆蛋白A或脂多糖的反应变化不一致。NPT 15392增强了杀伤细胞功能,包括T细胞介导的对同种异体肿瘤细胞的细胞毒性以及NK细胞对YAC-1肿瘤细胞的活性。根据给药时间,它对抗体包被的鸡红细胞(CRBC)的ADCC活性略有增强或抑制。关于NK细胞活性的刺激,静脉注射NPT 15392时对脾脏效应细胞的作用更明显,腹腔注射时对腹腔效应细胞的作用更明显。从这些结果来看,T辅助细胞、B细胞和NK细胞似乎是NPT 15392作用的靶细胞。根据所测试的免疫功能,各种刺激作用在不同时间达到峰值。此外,其作用的延长,有时出现双峰作用(对T细胞依赖性抗原的抗体反应、NK活性)表明其作用机制复杂,可能涉及由淋巴因子或单核因子介导的间接相互作用。