Polyamine deprivation prevents the development of tumour-induced immune suppression
Polyamine deprivation prevents the development of tumour-induced immune suppression
复制标题
DOI：
10.1038/bjc.1997.391
复制
发表时间：
1997-08-01
影响因子：
8.8
通讯作者：
Moulinoux, JP
中科院分区：
文献类型：
--
作者：
Chamaillard, L;CatrosQuemener, V;Moulinoux, JP
移植有3LL（刘易斯肺癌）的小鼠表现出免疫抑制：脾细胞显示自发性白细胞介素2（IL-2）产生减少以及T-CD 4（+）和T-CD 8（+）淋巴细胞群减少;此外，脾中多胺含量增加。通过用含有新霉素、甲硝唑和鸟氨酸脱羧酶和多胺氧化酶抑制剂的多胺缺乏饮食治疗小鼠，肿瘤生长减少，免疫异常逆转。脾细胞过度产生IL-2，通过减少外源性来源的多胺，但所有主要的多胺来源的总封锁是必要的，以获得最佳效果的IL-2的生产和脾多胺含量。无论多胺剥夺是否在肿瘤生长的早期或晚期开始，T淋巴细胞群恢复到正常值，表明多胺剥夺不仅可以防止肿瘤诱导的免疫抑制，而且可以逆转已建立的免疫紊乱。与所观察到的脾细胞产生IL-2和自然杀伤（NK）细胞活性相反，多胺氧化酶（PAO）抑制剂并没有增加T淋巴细胞的数量。这些发现与多胺对免疫效应细胞代谢的直接作用一致。他们建议的胃肠多胺和PAO活性的调节IL-2的生产中的重要作用。
Mice grafted with the 3LL (Lewis lung) carcinoma exhibit immune suppression: spleen cells showed decreased spontaneous interleukin 2 (IL-2) production and T-CD4(+) and T-CD8(+) lymphocyte populations; in addition the polyamine content in the spleen was increased. By treating the mice with a polyamine-deficient diet containing neomycin, metronidazole and inhibitors of ornithine decarboxylase and polyamine oxydase, tumour growth was reduced and the immune abnormalities were reversed. The spleen cells overproduced IL-2 by reducing exogenous sources of polyamines, but total blockade of all major polyamine sources was necessary to obtain an optimal effect both on IL-2 production and on spleen polyamine content. Irrespective of whether polyamine deprivation was started at an early or at an advanced stage of tumour growth, T-lymphocyte populations were restored to normal values, demonstrating that polyamine deprivation not only prevents tumour-induced immune suppression, but reverses established immunological disorders. In contrast to what was observed regarding IL-2 production by spleen cells and natural killer (NK) cell activity, the polyamine oxidase (PAO) inhibitor did not enhance the number of T lymphocytes. These findings are consistent with a direct effect of the polyamines on immune effector cell metabolism. They suggest an important role of the gastrointestinal polyamines and of PAO activity in the regulation of IL-2 production.