Study on the pathogenecity of tuberculosis in elderly people and development of its prevention

肺结核（TB）仍然是一个重要的问题，因为患有这种疾病的患者数量最近有所增加，特别是随着老年人的增加。本文分析了老年人结核病的发病机制，发现老年人结核病患者血清IL-12和IFN-γ水平较青年人有降低的趋势，而IFN-γ水平较青年人有降低的趋势。从这些数据可以看出，较低的Th 1免疫应答可能是老年人群中发生TB的原因之一。在进一步的研究中，我们利用加速衰老小鼠（SAM）建立了老年人结核病动物模型。这些小鼠在出生后5至6个月内比对照小鼠更早死亡。10月龄SAM小鼠肺、肝、脾细菌负荷量均显著高于同龄对照小鼠。但出生后3个月时，两组间上述器官中IFN-γ的浓度无显著差异。糖尿病（DM）是肺结核的重要危险因素，随着年龄的增长，DM患者的数量也在增加。因此，我们检测了结核病合并糖尿病患者、非糖尿病患者和健康对照者血清中IL-12和IFN-γ的水平。肺结核患者的上述值高于对照组，而糖尿病组显著低于非糖尿病组。此外，在通过链脲佐菌素建立的结核分枝杆菌感染的DM小鼠动物模型中也获得了类似的结果。本研究表明，老年人的结核病可能是在包括DM在内的各种病理条件引起的对结核分枝杆菌的Th 1免疫应答受损的基础上发生的。

Tuberculosis(TB) is still an important problem because the number of patients with this disease has recently been increased, especially with an increase in aged people. In the present study, we conducted an analysis on the pathogenecity of tuberculosis in this population, with a focus on the host immune responses.In TB in an aged group, serum levels of IL-12 and IFN-γ tended to be and were significantly lower than in a younger group, respectively. From these data, it was suggested that lower Th1 immune responses could be one of the reasons for the development of TB in the aged population. In further study, we established an animal model of TB in aged people using senescence accelerated mice(SAM). These mice showed a tendency in the earlier death of this infection from 5 to 6 months after birth than control mice. The bacterial loads in lung, liver and spleen were significantly higher in 10 months-old SAM mice than in control mice with the same age. However, there was no significant difference in the concentrations of IFN-γ in these organs between two groups at 3 months after birth.The number of patients with diabetes mellitus(DM), an important risk factor of TB, is known to increase with aging. Therefore, we measured the serum levels of IL-12 and IFN-γ in TB patients complicated with and not with DM and healthy control subjects. Such values were increased in TB patients compared to control subjects, which were significantly lower in DM group than in non-DM group. In addition, similar findings were obtained in an animal model of DM mice infected with Mycobacterium tuberculosis, which were established by administration of streptozotocin.The present study suggested that TB in aged people could be developed on the basis of the impairment of Th1 immune responses to M.tuberculosis caused by various pathological conditions, including DM.