Soluble form of Fas and Fas ligand in BAL fluid from patients with pulmonary fibrosis and bronchiolitis obliterans organizing pneumonia

Study objectives: The Fas-Fas ligand (FasL) pathway is a representative sys tem of apoptosis-signaling receptor molecules. We previously described that this pathway may play an important role in the pathogenesis of fibrosing l ung diseases. In this study, we hypothesized that soluble form of Fas (sFas ) and Fast (sFasL) may also be associated with this disorder. Measurements and results: We measured sFas and sFasL levels in BAL fluid (B ALF) from patients with idiopathic pulmonary fibrosis (IPF), interstitial p neumonia associated with collagen vascular diseases (CVD-IP), and bronchiol itis obliterans organizing pneumonia (BOOP), using enzyme-linked immunosorb ent assay. BALF from all patients was obtained before prednisolone therapy. sFasL levels were relatively increased in IPF patients (p = 0.084), and si gnificantly increased in CVD-IP patients (p < 0.05) and BOOP patients (p < 0.05), compared with control subjects, BALF sFasL levels were elevated in t he IPF or CVD-IP subgroups with an indication for prednisolone therapy, com pared with those without an indication for therapy. The BALF sFasL level in IPF patients was correlated with the number of total cells and lymphocytes . The BALF sFasL level in BOOP patients was relatively or significantly cor related with the number of total cells or lymphocytes, respectively. The BA LF sFas level was significantly increased in BOOP patients, but not in IPF or CVD-IP patients. Conclusions: We conclude that BALF sFasL levels may be associated with the accumulation of inflammatory cells and reflect the degree of lymphocyte alv eolitis in IPF. The elevation of sFasL may be associated with the deteriora tion of IPF and CVD-IP. The elevation of the BALF sFas level may abrogate t he cytotoxicity of FasL in BOOP patients, which may be associated with bett er prognosis of BOOP, compared with IPF or CVD-IP.