Bruley-Rosset M, Florentin I, Kiger N, Schulz J I, Mathé G
Recent Results Cancer Res. 1980;75:139-46. doi: 10.1007/978-3-642-81491-4_22.
An attempt to correct the impaired immune functions of aged mice was made by injecting repeatedly (over a 6-month period) two chemically defined immunostimulating agents, levamisole and bestatin, into 12- to 16-month-old hybrid mice. Continuous treatment with levamisole restored T-cell-dependent functions (delayed-type hypersensitivity reaction and antibody response to T-dependent antigens) and prevented the appearance of suppressor cells induced by aging. In aged animals, this treatment led to macrophage activation and to a significant reduction of ADCC activity near the baseline value of young animals. Weekly injections of bestatin resulted in varying effects, depending on the dose administered. Small doses (10 microgram/injection) were more effective in restoring humoral response to SRBC rather than delayed-type hypersensitivity reaction, whereas large doses (100 microgram/injection) had the opposite effect. Macrophage activation was obtained only after the administration of the high dose of bestatin. Continuous treatment with bestatin did not eliminate suppressor cell activity, but decreased the ADCC normally elevated in aged animals. A significant reduction of spontaneous tumors and prolongation of median survival was observed in mice given repeated injections of levamisole and of 100 microgram bestatin, compared with untreated aged mice and with mice given low doses of bestatin.
通过在6个月的时间内反复给12至16月龄的杂种小鼠注射两种化学组成明确的免疫刺激剂——左旋咪唑和贝司他汀，来尝试纠正老龄小鼠受损的免疫功能。持续用左旋咪唑治疗可恢复T细胞依赖性功能（迟发型超敏反应和对T细胞依赖抗原的抗体反应），并防止衰老诱导的抑制细胞出现。在老龄动物中，这种治疗导致巨噬细胞活化，并使抗体依赖细胞介导的细胞毒性（ADCC）活性显著降低至接近年轻动物的基线值。每周注射贝司他汀会产生不同的效果，这取决于给药剂量。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）则有相反的效果。只有在给予高剂量贝司他汀后才出现巨噬细胞活化。持续用贝司他汀治疗并未消除抑制细胞活性，但降低了老龄动物中通常升高的ADCC活性。与未治疗的老龄小鼠和给予低剂量贝司他汀的小鼠相比，反复注射左旋咪唑和100微克贝司他汀的小鼠自发肿瘤显著减少，中位生存期延长。
