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。在本研究中，我们对该人群结核病的发病机制进行了分析，重点是宿主免疫反应。在老年组结核病患者中，血清IL-12和干扰素-γ水平分别倾向于和显著低于年轻组。提示Th1免疫功能低下可能是老年人群结核病发病的原因之一。在进一步的研究中，我们利用衰老加速小鼠(SAM)建立了老年人结核病的动物模型。这些小鼠在出生后5~6个月表现出比对照小鼠更早死亡的趋势。10月龄SAM组小鼠肺、肝、脾的细菌载量显著高于同龄对照组。然而，在出生后3个月，两组患者体内干扰素-γ的浓度没有显著差异。糖尿病(DM)患者的数量已知随着年龄的增长而增加。糖尿病(DM)是结核病的重要危险因素。因此，我们检测了合并和不合并糖尿病的肺结核患者和健康对照组的血清IL-12和干扰素-γ水平。与对照组相比，肺结核病患者上述指标明显升高，而糖尿病组显著低于非糖尿病组。此外，在用链脲佐菌素建立的糖尿病小鼠感染结核分枝杆菌的动物模型上也得到了类似的结果。本研究表明，老年结核病可能是在包括糖尿病在内的各种病理条件下引起的对结核分枝杆菌Th1免疫反应障碍的基础上发生的。

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.