Open AccessFibroblast growth factors in connective tissue disease associated interstitial lung disease
Author(s) -
THORNTON S. C.,
ROBBINS J. M.,
PENNY R.,
BREIT S. N.
Publication year - 1992
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1992.tb05866.x
Subject(s) - connective tissue , bronchoalveolar lavage , growth factor , pulmonary fibrosis , platelet derived growth factor , interstitial lung disease , medicine , fibrosis , ctgf , platelet derived growth factor receptor , immunology , connective tissue disease , fibroblast , lung , tumor necrosis factor alpha , population , basic fibroblast growth factor , pathology , biology , autoimmune disease , antibody , cell culture , genetics , receptor , environmental health
SUMMARY Fibrosis is a major cause of morbidity and mortality in chronic inflammatory diseases, especially interstitial pulmonary disorders. Fibroproliferation is an important part of this fibrotic response, and is mediated largely through growth factors such as platelet‐derived growth factor (PDGF), insulin‐like growth factor (IGF) I and tumour necrosis factor‐alpha (TNF‐α). Although there is some evidence implicating these cylokines in fibrotic disorders, strong evidence in vivo is almost nonexistent. In order to ascertain the role that these factors play in inflammatory lung disorders associated with connective tissue diseases, alveolar mononuclcar cells have been obtained from subjects by bronchoalveolar lavage and assessed for the spontaneous release of fibroblast growth factors. The study population consisted of subjects with a variety of different connective tissue disorders, both with and without inflammatory pulmonary complications. It was found that lavage cells spontaneously secreted fibroblast growth factor activity over 24 h with maximum activity detected at 6 to 12 h. Growth factor activity could be detected in most subjects with connective tissue disease‐associated inflammatory lung disease and some normal subjects, but the amount of growth factor activity was much higher in the former than in the latter. By means of antibody depletion experiments all growth factor activity from lavage cells of normal patients was attributable to TNF‐α while patients with interstitial lung disease secreted large amounts of PDGF and fibronectin in addition to TNF‐α. Approximately 40–50% of the total released growth factor activity could be accounted for by PDGF, and 100% by the combination of PDGF. TNF‐α and fibronectin. While TNF‐α is released from the bronchoalveolar lavage cells of many subjects, in addition, many patients with interstitial lung disease also release spontaneously, large amounts of fibroblast growth factor activity attributable to PDGF and fibronectin.