Modulation of cytokine expression represents a potentially useful approach for the treatment of idiopathic pulmonary fibrosis (IPF).To identify potential targets for such intervention, semi-quantitative reverse transcriptasepolymerase chain reaction was used to compare the expression of messenger ribonucleic acids (mRNAs) coding for 17 cytokines in lung tissue obtained from patients with IPF at the time of diagnosis and control subjects. Some cytokines were also studied at the protein level by immunohistochemical techniques.mRNAs coding for all of the cytokines evaluated were detected in both control and fibrotic lung samples. Only transforming growth factor (TGF)-b and interleukin (IL)-10 mRNAs were quantitatively increased in lung biopsies from patients with IPF compared with those of controls, results confirmed at the protein level by immunohistochemistry. Although mRNAs for platelet-derived growth factor (PDGF)-BB and keratinocyte growth factor (KGF) were expressed in similar amounts in lungs from patients with IPF and controls, localised accumulation of both factors was also observed in IPF. Hyperplastic alveolar epithelial cells were a prominent source of cytokines, where IL-10, PDGF-BB and KGF were present in increased amounts, although increased accumulation in fibroblasts, smooth-muscle cells and matrix components was also observed (PDGF-BB, TGF-b).These results offer new insights into the cytokines produced in the lung in idiopathic pulmonary fibrosis and suggest that modulation of the production of transforming growth factor-b and interleukin-10 may represent a potentially useful therapeutic strategy for this disabling disease.
High-resolution computed tomography (HRCT) has proved to be very useful in the diagnosis and follow-up of pulmonary Langerhans cell histiocytosis (PLCH), but the precise relationships between nodules and thin-wall cysts observed by HRCT, and granulomatous or cystic lesions present in lung tissue, remain to be established. The aim of this study was to compare quantitative data obtained by HRCT and those obtained by histopathological examination of corresponding lung tissue specimens in patients with biopsy-proven PLCH. The results demonstrated that the extent of nodular abnormalities was strongly correlated with the density of florid granulomatous lesions in lung tissue. A strong correlation was also found between the extent of cystic abnormalities and the density of cavitary lesions, but the latter included both still inflammatory cavitary granulomas and cicatricial fibrous cysts. Interestingly, small isolated florid granulomas were found in lung tissue from most patients with a predominant cystic CT scan pattern. Taken together, these results demonstrate that HRCT has to be considered with caution to evaluate the histopathological activity of PLCH. Patients presenting with predominant HRCT cystic abnormalities should benefit from a long-term follow-up. Because these patients are susceptible to developing severe respiratory insufficiency, they should also be considered for treatment as soon as an effective therapy for LCH is available.
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