Fibroblast-alveolar cell interactions in sarcoidosis and idiopathic pulmonary fibrosis: Evidence for stimulatory and inhibitory cytokine production by alveolar cells

Abstract

To better understand how the activity of inflammatory cells collected by bronchoalveolar lavage (BAL) could affect the outcome of granulomatous and fibrotic pulmonary diseases, we studied secretory products and messenger ribonucleic acid (mRNA) expression for certain cytokines of BAL cells in 10 controls, 14 patients with interstitial pulmonary fibrosis (IPF) and 22 patients with sarcoidosis. We assayed the activity of 48 h conditioned media for: 1) their biological action on fibroblast proliferation and prostaglandin E2 (PGE2), collagenase and collagen production by fibroblasts; 2) TNF(α) levels by bioassay and radioimmunoassay; 3) interleukin 1 (IL-1) α and β and β levels by solid phase enzyme immunoassay (EIA); 4) tumour necrosis factor (TNF) and IL-1 inhibitory activity. We also measured, in freshly isolated BAL cells: 1) mRNA levels for IL-1α and β and TNF(α); 2) cell-associated IL-1α and β by EIA. The only difference found in the assessment of the biological activity of BAL cells conditioned medium was an increase in fibroblast proliferation in sarcoidosis vs IPF patients. The IL-1α and β, and TNF(α) contents of conditioned media were similar in the three groups. Inhibitory activity against IL-1 and TNF(α) was found in a few patients. Further analysis revealed two peaks of inhibitory activity against IL-1 (20-25 kD and 35-40 kD), as well as a distinct TNF(α) inhibitory activity which could be retained on a TNF(α)-binding affinity column. No mRNA expression for TNF(α) and β was found in freshly isolated BAL cells, whereas very variably levels of IL-1α and β mRNA levels were detected in the three groups. Because of these variable results of differences in functional state between freshly isolated and cultured BAL cells, and of the presence of inhibitory substances against IL-1 and TNF(α), it is unlikely that the development of fibrosis could be ascribed to a single disorder or abnormality.