• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.506-518
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• 2002

Background : There have been several studies showing that angiotensin II and the angiotensin converting enzyme (ACE) contribute to the activation of fibroblast including the pulmonary fibrosis, and apoptosis of the alveolar epithelium in idiopathic intersititial pneumonia. This study was performed to identify the relationship between the serum angiotensin II, ACE and the pulmonary function test (PFT), the dyspnea score, and the cell fraction of the bronchoalveolar lavage fluid(BALF). Materials and Methods : Twenty three patients with idiopathic interstitial pneumonia from March, 1999 to October, 2001 at Gachon medical school were enrolled in this study. They were divided into IPF(UIP) (16) and NSIP (7) groups. Twelve of the idiopathic interstitial pneumonia patients (UIP : 5, NSIP : 7) were diagnosed by an open lung biopsy, 11 of IPF patients were diagnosed by the American Thoracic Society (ATS) diagnostic criteria. The PFT values, dyspnea score, serum ACE and angiotensin II were measured, and a bronchoscopy was performed to obtain the BALF. Results : Of all the patients, 7 were in the normal range and 14 showed an increase in the serum level of angiotensin II. In terms of the serum ACE level, 14 patients had an increased level. The DLCO% of the angiotensin II in increased group was significantly lower than the not-increased group (p=0.021). Other factors did not correlate with the serum ACE or the angiotensin II increased group and not-increased group. Conclusion : These results suggest that an increased angiotensin II serum level may be associated with increase in the of alveolar capillary block in the progression of pulmonary fibrosis in idiopathic interstitial pneumonia.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.871-888
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• 1997

Background : It is now thought that the earliest manifestation of idiopathic pulmonary fibrosis is alveolitis, that is, an accumulation of inflammatory and immune effector cells within alveolar walls and spaces. Inflammatory cells including alveolar macrophages and resident normal pulmonary tissue cells participate through the release of many variable mediators such as inflammatory growth factors and cytokines, which contribute to tissue damage and finally cause chronic pulmonary inflammation and fibrosis. This study was performed to investigate the source and distribution pattern of transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), platelet derived growth factor(PDGF), basic fibroblast growth factor(bFGF), interleukin 1(IL-1), interleukin 6(IL-6), tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and the role of these mediators on bleomycin(BLM)-induced pulmonary injury and fibrosis in rats. Method : Wistar rats were divided into three groups(control group, BLM treated group, BLM and vitamine E treated group). Animals were sacrificed periodically at 1, 2, 3, 4, 5, 7, 14, 21, 28 days after saline or BLM administration. The effects were compared to the results of bronchoalveolar lavage fluid analysis, light microscopic findings, immunohistochemical stains for six different mediators(TGF-${\beta}_1$, PDGF, bFGF, IL-1, IL-6 and TNF-$\alpha$) and mRNA in situ hybridization for TGF-${\beta}_1$. Results : IL-1 and IL-6 are maximally expressed at postbleomycin 1~7th day which are mainly produced by neutrophils and bronchiolar epithelium. It is thought that they induce recruitment of inflammatory cells at the injury site. The expression of IL-1 and IL-6 at the bronchiolar epithelium within 7th day is an indirect evidence of contribution of bronchiolar epithelial cells to promote and maintain the inflammatory and immune responses adjacent to the airways. TNF-$\alpha$ is mainly produced by neutrophils and bronchiolar epithelial cells during 1~5th day, alveolar macrophages during 7~28th day. At the earlier period, TNF-$\alpha$ causes recruitment of inflammatory cells at the injury site and later stimulates pulmonary fibrosis. The main secreting cells of TGF-${\beta}_1$ are alveolar macrophages and bronchiolar epithelium and the target is pulmonary fibroblasts and extracellular matrix. TGF-${\beta}_1$ and PDGF stimulate proliferation of pulmonary fibroblasts and TGF-${\beta}_1$ and bFGF incite the fibroblasts to produce extracellular matrix. The vitamine E and BLM treated group shows few positive cells(p<0.05). Conclusion : After endothelial and epithelial injury, the neutrophils and bronchiolar epithelium secrete IL-1, IL-6, TNF-$\alpha$ which induce infiltration of many neutrophils. It is thought that variable enzymes and $O_2$ radicals released by these neutrophils cause destruction of normal lung architecture and progression of pulmonary fibrosis. At the 7~28th day, TGF-${\beta}_1$, PDGF, bFGF, TNF-$\alpha$ secreted by alveolar macrophages sting pulmonary fibroblasts into proliferating with increased production of extracellular matrix and finally, they make progression of pulmonary fibrosis. TNF-$\alpha$ compares quite important with TGF-${\beta}_1$ to cause pulmonary fibrosis. Vitamine E seems to decrease the extent of BLM induced pulmonary fibrosis.