| Project/Area Number |
12670552
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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 |
Respiratory organ internal medicine
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| Research Institution | Tokyo Medical & Dental University |
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Principal Investigator |
YOSHIZAWA Yasuyuki Tokyo Medical & Dental University, 大学院・医歯学総合研究科, 教授 (20174914)
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| Co-Investigator(Kenkyū-buntansha) |
INASE Naohiko Tokyo Medical & Dental University, 医学部・附属病院, 講師 (60262185)
MIYZKE Shuji Tokyo Medical & Dental University, 保健管理センター, 助教授 (50239365)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | chronic hypersensitivity pneumonitis / recurrent / insidious / idiopathic pulmonary fibrosis / antigen-induced lymphocyte proliferation / specific antibody / HRCT / honeycomb / genetic background / Interleukin 10 / 免疫グロブリンサブクラス / IL-2RmRNA / 吸入誘発試験 / リンパ球幼弱化試験 / 合成ペプタイド |
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| Research Abstract |
Our manuscript claiming that chronic hypersensitivity pneumonitis should be subgrouped into two types, one subgroup of patients develops interstitial pulmonary fibrosis after recurrent acute episodes (recurrent) and the other group of patients has no history of acute episodes that has a slowly progressive chronic respiratory disease (insidious) has been accepted in Am Asthma Allergy Immunology. The recurrent bird fancier's lung (BFL) patients tended to breed dozens of pigeons in a loft, specific antibodies against pigeon dropping extracts were positive in 87%, antigen-induced lymphocyte proliferation was positive in 93%, bronchoalveolar lavage fluids (BALF) showed lymphocytosis, and centrilobular micronodules were observed on chest high resolution computer tomography (HRCT) in 40%. Those findings are similar to those of acute BFL. In contrast, the insidious BFL patients were likely to be exposed to smaller sized birds kept indoors, clubbed fingers were observed in 53%, specific antibod
… More
ies against pigeon dropping extracts or budgerigar dropping extracts were positive in only 35% showing that the remaining 65% patients were negative. In contrast, antigen-induced lymphocyte proliferation was positive in 94%. BALF showed normal ranges or a slight increase of lymphocytes, HRCT displayed centrilobular micronodules in only 12% and honeycombing in 88%. Histopathological findings on surgically obtained specimens revealed UIP pattern in 8 cases out of 12 cases. All those clinico-pathological features were similar to IPF. The mechanisms involved in the progression of disease process leading to fibrosis after avoidance of direct antigen contacts are under investigation implicating that indirect exposure to birds and/or the persistence of antigen in the lung may be responsible for ensuing pulmonary fibrosis. Currently, the genetic background of the patients who are susceptible to developing pulmonary fibrosis are under investigation. Furthermore, we have explored the mechanisms involved in the initiation of acute HP as compared to protection from disease in asymptomatic counterparts with current exposure. Peripheral blood mononuclear cells from HP patients proliferated in the presence of the antigen and showed enhanced expression of mRNA of proinflammatory cytokines including IL-β and IL-6 as well as IL-2R. In contrast, normal volunteers with current exposure showed elevated levels of mRNA expression of IL-10 and IL-2R suggesting the presence of sensitized cells and protection from pathology as a result of enhanced production of IL-10. These results implicated that IL-10 is inhibitory for the onset of HP and is the key determinant as to whether the disease develops or not. Less
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