Bruley-Rosset M, Florentin I, Kiger N, Schulz J, Mathé G
Immunology. 1979 Sep;38(1):75-83.
An attempt to correct the state of immunodeficiency in old age was made by repeatedly injecting a chemically defined immunostimulating agent, bestatin, to 16 month old (C57Bl/6 x BALB/c) F1 mice. Aged mice were found to have depressed T-cell and B-cell responses but increased ADCC activity. Weekly injections of bestatin over a period of 6 months resulted in varying effects depending on the dose administered. Small doses (10 microgram per injection) were more effective in restoring humoral responses to SRBC rather than delayed-type hypersensitivity reactions, whereas large doses (100 microgram per injection) acted in the opposite way. Macrophage activation was only obtained after the administration of the high doses of bestatin. Continuous treatment with bestatin did not prevent the appearance of suppressor cells induced by ageing. It led to a significant reduction of ADCC activity in aged animals near to the base line value of young animals. Animals were examined for the presence of spontaneous tumours from the end of the treatment until the age of 28 months. A significant reduction of spontaneous tumour incidence was observed in mice given repeated injections of 100 microgram bestatin when compared to untreated aged mice and to mice given the low doses of bestatin.
通过向16月龄的（C57Bl/6×BALB/c）F1小鼠反复注射一种化学定义明确的免疫刺激剂——贝司他汀，来尝试纠正老年小鼠的免疫缺陷状态。研究发现老年小鼠的T细胞和B细胞反应受到抑制，但抗体依赖的细胞介导的细胞毒性（ADCC）活性增强。在6个月的时间里每周注射贝司他汀，根据给药剂量的不同会产生不同的效果。小剂量（每次注射10微克）在恢复对绵羊红细胞（SRBC）的体液反应方面比恢复迟发型超敏反应更有效，而大剂量（每次注射100微克）的作用则相反。只有在给予高剂量的贝司他汀后才能激活巨噬细胞。持续用贝司他汀治疗并不能阻止衰老诱导的抑制细胞的出现。它使老年动物的ADCC活性显著降低，接近年轻动物的基线值。从治疗结束到28月龄，对动物进行自发性肿瘤检查。与未治疗的老年小鼠和给予低剂量贝司他汀的小鼠相比，反复注射100微克贝司他汀的小鼠的自发性肿瘤发生率显著降低。
