In vivo levels and in vitro production of interferon-gamma in fibrosing interstitial lung diseases

Abstract

The in vivo role of interferons in the development of fibrosis is not fully understood but it is known that interferons can suppress fibroblast proliferation and collagen synthesis in vitro. We have recently demonstrated that in a group of patients with sarcoidosis having predominant pulmonary involvement, patients with the highest levels of circulating interferon-gamma (IFN-gamma) more frequently resolved on corticosteroids, suggesting that they had a less 'fibrotic' component to their disease. We now report that in two other diseases, where the tendency to develop pulmonary fibrosis is greater than in sarcoidosis, namely cryptogenic fibrosing alveolitis (CFA) and fibrosing alveolitis associated with the systemic connective tissue disease progressive systemic sclerosis (FA + PSS), very few patients have elevations in IFN-gamma in their serum. However, as in sarcoidosis, those with the highest levels responded to corticosteroids (P less than 0.05). Attempts to measure IFN-gamma levels in the lungs, using cell-free bronchoalveolar lavage (BAL) fluid supernatants, were negative in all the study groups, suggesting that these samples may be inadequate for such studies. To investigate whether there might be an intrinsic defect in T lymphocyte function associated with predisposition to fibrosing lung diseases, we then investigated the in vitro production of IFN-gamma by lymphocytes separated from the blood of 18 untreated patients (six with CFA, six with FA + PSS and six with sarcoidosis). IFN-gamma production was impaired in 10 (56%) (two with CFA, four with FA + PSS and four with sarcoidosis). A higher proportion of the fibrosing alveolitis patients (CFA or FA + PSS) with impaired IFN-gamma production have subsequently shown spontaneous lung functional deterioration. These findings suggest that impaired IFN-gamma release might be a potentiating factor in the pathogenesis of these fibrosing lung diseases.