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

结核病（TB）仍然是一个重要的问题，因为患有这种疾病的人数最近有所增加，特别是老年人的增加。在本研究中，我们对该人群中结核病的致病性进行了分析，重点关注宿主的免疫反应。在老年结核患者中，血清IL-12和IFN-γ水平分别倾向于和显著低于年轻组。这些数据表明，较低的Th1免疫反应可能是老年人群中结核病发展的原因之一。在进一步的研究中，我们用衰老加速小鼠（senescence accelerated mice， SAM）建立了老年人结核动物模型。这些小鼠在出生后5到6个月的感染中表现出比对照组小鼠更早死亡的趋势。10月龄SAM小鼠肺、肝、脾细菌负荷显著高于同龄对照组。然而，出生后3个月，两组之间这些器官中IFN-γ的浓度没有显著差异。糖尿病是结核病的一个重要危险因素，随着年龄的增长，糖尿病患者的数量也在增加。因此，我们测量了合并和不合并糖尿病的结核病患者以及健康对照者的血清IL-12和IFN-γ水平。与对照组相比，结核病患者的这一数值有所增加，而糖尿病组的这一数值明显低于非糖尿病组。此外，通过给药链脲佐菌素建立的感染结核分枝杆菌的DM小鼠动物模型也得到了类似的结果。本研究提示，老年人结核病可能是基于多种病理条件（包括糖尿病）导致的对结核分枝杆菌的Th1免疫应答受损而发展起来的。

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.