Transforming growth factor-beta1 in sarcoidosis

Abstract

Transforming growth factor-P (TGF-P) is a cytokine that promotes extracellular matrix accunlulation and inhibits matrix degradation. Although the natural course of sarcoidosis is usually favourable, g~anuloma healing in the lung may result in pulmonary fibrosis and respiratory impairment in some patients. In this study TGF-PI was evaluated in bronchoalveolar lavage (BAL) fluid and cul- ture supernatants of alveolar macrophages (AM) from 73 patients with hiopsy- proven sarcoidosis. Diseasc activity was defined when patients recently developed or increased symptoms (cough, dyspnoea, systemic symptoms) andlor demonstrated increasing opacities on chest radiography. Pulnlonary function tests were performed in all patients including forced expiratory volunle in one second (FEVI), forced vital capacity (FVC), total lung capacity (TLC) and the diffusing capacity of the lung for carbon n~onoxide (DL,co). Fourteen patients with idiopathic pulmonary fibrosis (IPF) and 14 healthy subjects were investigated as a control group. In~munohistochenlistry was used to evaluate the cell distribution of TGF-PI on lung specinlens. TGF-PI levels in BAL and in AM supernatants were not different between sar- coidosis and healthy subjects, whereas they were markedly increased in IPE How- ever, the TGF-PI level was significantly increased in BAL fluid but not in AM supernatants from sarcoidosis with altered lung function, compared with patients with normal lung function. The TGF-P, level in BAL was increased in active sarcoido- sis but this increased level was mainly related to the higher level observed in patients with altered lung function. TGF-PI levels in BAL correlated significantly with the lymphocyte percentage. TGF-PI staining assessed hy immunohistochemistry was intense in epithelioid histiocytes comprising non-necrotizing granuloma and in bron- chiolar epithelial cells, in hyperplastic type I1 pneunlocytes and occasionally in AM. This study supports the hypothesis that overproduction of transforming growth factor-Dl is associated with functional impairment in patients with pulmonary sar- coidosis. Ezrr Respir J 1998: 12: 913-919. *Service de Pneurnologie et Irnrnuno- Allergologie and '"Laboratoire d'Anatopa- thologie, HBpital Calmette CH et U Lille, France. +Laboratoire de Pathologie Irnmu- noAllergique Respiratoire, et Cellules Infl- ammatoires INSERM Unit6 416, lnstitut Pasteur Lille, France. Correspondence: B Wallaert Clin~que des Maladies Respiratoircs HBpital Calmette CH et U de Lille 59037 Lille Cedex France Fax: 33 320446693

Key Biomarkers

Symptom Clusters