| Project/Area Number |
15591061
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
SAITO Atsushi University of the Ryukyus, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (90039842)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAKAMI Kazuyoshi University of the Ryukyus, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (10253973)
HIGA Futoshi University of the Ryukyus, Graduate School of Medicine, Assistant Professor, 大学院・医学研究科, 助手 (50291555)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | tuberculosis / aged people / diabetes mellitus / IFN-γ / IL-12 / senescence accelerated mice / diabetic mice / Th1反応 / 内因性再燃 / Th1サイトカイン |
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| Research Abstract |
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.
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