Alveolar macrophages in idiopathic pulmonary fibrosis have glucocorticoid receptors, but glucocorticoid therapy does not suppress alveolar macrophage release of fibronectin and alveolar macrophage derived growth factor.
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Although glucocorticoids are the most widely used therapeutic modality in the treatment of idiopathic pulmonary fibrosis (IPF), the administration of these agents infrequently arrests the progressive fibrosis of this disorder. In this context, the present study was designed to determine if the lack of effect of glucocorticoid therapy in IPF could be explained, in part, by a lack of effect of glucocorticoids on alveolar macrophage release of fibronectin and alveolar macrophage derived growth factor (AMDGF), mediators thought to play a role in the accumulation of fibroblasts associated with the fibrosis of this disease. Patients with IPF were studied in 2 groups, those receiving glucocorticoid therapy and those not receiving therapy. The release of fibronectin by alveolar macrophages of IPF patients was elevated compared to release of fibronectin from alveolar macrophages obtained from normal volunteers (p less than 0.01). However, the release of fibronectin was no different in treated and untreated patients with IPF (p greater than 0.2). Like fibronectin, the release of AMDGF by alveolar macrophages of IPF patients was elevated compared to release of AMDGF from alveolar macrophages obtained from normal volunteers (p less than 0.01), but there was no difference in treated and untreated IPF patients (p greater than 0.2). Sequential evaluation of IPF patients before and after glucocorticoid therapy demonstrated no impact of glucocorticoid therapy on alveolar macrophage release of fibronectin and AMDGF. The inability of glucocorticoids to suppress fibronectin and AMDGF release was not due to a lack of glucocorticoid receptors in IPF patients because alveolar macrophages from patients and from normal volunteers bound glucocorticoids similarly.(ABSTRACT TRUNCATED AT 250 WORDS)