Hadden J W, Hadden E M, Spira T, Settineri R, Simon L, Giner-Sorolla A
Int J Immunopharmacol. 1982;4(3):235-42. doi: 10.1016/0192-0561(82)90053-4.
NPT 15392 (Erythro-9 (2-hydroxy-3 nonyl) hypoxanthine), a novel heterocyclic immunomodulatory compound, was analyzed over a broad concentration range on a variety of human blood leukocyte functions in vitro. NPT 15392 augmented mitogen-induced lymphocyte transformation in a variable fashion; lymphocytes from 9 of 24 individuals showed significant stimulation with phytohemagglutinin at 0.01 microgram/ml of NPT 15392, and 3 of 14 and 3 of 3 showed similar augmentation with concanavalin A and pokeweed mitogen, respectively. NPT 15392 above 10 microgram/ml inhibited mitogen responses and did not itself stimulate cell division. NPT 15392 also augmented responses of lymphocytes to antigenic stimulation with Candida and Staphylococcus antigens, purified protein derivative, and allogeneic cells in a variable manner. When observed, stimulation occurred at 0.01-1 microgram/ml of NPT 15392 for Candida and Staph. and at 0.01 microgram/ml with PPD and allogeneic cells. NPT 15392 (0.01-1 microgram/ml) consistently induced suppressor cell function alone and in combination with concanavalin A. This effect is apparently mediated by T lymphocytes since suppression was not mediated by interferon, prostaglandin or histamine. In addition, NPT 15392 (0.01-10 microgram/ml) significantly augmented "active" T cell rosettes. NPT 15392 over a broad concentration range and in the presence and absence of interferon did not stimulate natural killer cell activity or antibody-dependent cellular cytotoxicity. The data indicate that NPT 15392 is a modulator of such T lymphocyte functions as proliferative response to antigen and mitogen, suppressor activity and receptor display. Such activities imply potential therapeutic use in immunodeficiency related to defects of the thymus and thymus-derived lymphocytes.
NPT 15392（赤藓红-9（2-羟基-3-壬基）次黄嘌呤）是一种新型杂环免疫调节化合物，在体外对多种人类血液白细胞功能进行了广泛浓度范围的分析。NPT 15392以可变方式增强有丝分裂原诱导的淋巴细胞转化；24名个体中有9名个体的淋巴细胞在0.01微克/毫升的NPT 15392作用下，对植物血凝素表现出显著刺激，14名个体中有3名以及3名个体中的3名分别对刀豆球蛋白A和商陆有丝分裂原表现出类似的增强作用。浓度高于10微克/毫升的NPT 15392抑制有丝分裂原反应，且本身不刺激细胞分裂。NPT 15392还以可变方式增强淋巴细胞对抗原刺激的反应，抗原刺激物包括念珠菌、葡萄球菌抗原、纯化蛋白衍生物和同种异体细胞。观察到刺激作用时，念珠菌和葡萄球菌抗原在0.01 - 1微克/毫升的NPT 15392作用下出现，纯化蛋白衍生物和同种异体细胞在0.01微克/毫升的NPT 15392作用下出现。NPT 15392（0.01 - 1微克/毫升）单独以及与刀豆球蛋白A联合使用时，持续诱导抑制细胞功能。这种效应显然由T淋巴细胞介导，因为抑制作用不是由干扰素、前列腺素或组胺介导的。此外，NPT 15392（0.01 - 10微克/毫升）显著增强“活性”T细胞玫瑰花结形成。在广泛的浓度范围内，无论有无干扰素存在，NPT 15392均不刺激自然杀伤细胞活性或抗体依赖性细胞毒性。数据表明，NPT 15392是T淋巴细胞功能的调节剂，这些功能包括对抗原和有丝分裂原的增殖反应、抑制活性以及受体展示。这些活性意味着它在与胸腺和胸腺来源淋巴细胞缺陷相关的免疫缺陷中具有潜在的治疗用途。
