| Budget Amount *help |
¥17,750,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2007: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2006: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Research Abstract |
COPD is a disorder with several coexisting symptoms, and these symptoms are known to influence the prognosis of any individual COPD patient. Common coexisting symptoms include arterial sclerosis, hypertension, cor pulmonale and right heart failure, other cardiovascular system lesions, hyperlipemia, diabetes mellitus, osteoporosis, emaciation, and depression. Therefore, treatment of COPD needs to consider pulmonary symptoms in addition to other co-existing conditions.
We previously reported that pulmonary inflammation in patients with severe COPD was not improved by the cessation of smoking. In our studies, we found that the cytokine Interleukin-18 (IL-18) was strongly expressed in alveolar macrophages, CD8^+ T cells, and both the bronchiolar and alveolar epithelia in the lungs of COPD patients. In mice, constitutive IL-18 overproduction in the lungs resulted in pulmonary inflammation with the appearance of CD8^+ T cells, macrophages, neutrophils, and eosinophils. Enlarged lung volume, severe emphysematous change, dilatation of the right ventricle, and mild pulmonary hypertension were observed in aged IL-18 Tg mice. Based on these finding, we hypothesize that IL-18 may contribute to the onset / development of the coexistence symptoms of COPD. We previously determined that thioredoxin1 (TRX1) inhibits elastase-induced pulmonary inflammation and emphysematous changes in a mouse model. We will utilize the elastase-induced emphysema model in order to determine if TRX1 represents a possible new treatment of the coexisting symptoms in COPD.
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