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Clinical Investigations: IMMUNOLOGY |

Soluble Form of Fas and Fas Ligand in BAL Fluid From Patients With Pulmonary Fibrosis and Bronchiolitis Obliterans Organizing Pneumonia*

Kazuyoshi Kuwano, MD, PhD; Masayuki Kawasaki, MD, PhD; Takashige Maeyama, MD; Naoki Hagimoto, MD, PhD; Norio Nakamura; Kamon Shirakawa; Nobuyuki Hara, MD, PhD, FCCP
Author and Funding Information

*From the Research Institute for Diseases of the Chest (Drs. Kuwano, Kawasaki, Maeyama, Hagimoto, and Hara), Graduate School of Medical Sciences, Kyushu University, Fukuoka; and Bioscience Laboratory Research Center (Mr. Nakamura and Mr. Shirakawa), Mochida Pharmaceutical Company, LTD, Tokyo, Japan.

Correspondence to: Kazuyoshi Kuwano, MD, PhD, Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, 3–1-1 Maidashi, Higashiku, Fukuoka, 812 Japan; e-mail: kkuwano@kokyu.med.kyushu-u.ac.jp



Chest. 2000;118(2):451-458. doi:10.1378/chest.118.2.451
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Study objectives: The Fas-Fas ligand (FasL) pathway is a representative system of apoptosis-signaling receptor molecules. We previously described that this pathway may play an important role in the pathogenesis of fibrosing lung diseases. In this study, we hypothesized that soluble form of Fas (sFas) and FasL (sFasL) may also be associated with this disorder.

Measurements and results: We measured sFas and sFasL levels in BAL fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF), interstitial pneumonia associated with collagen vascular diseases (CVD-IP), and bronchiolitis obliterans organizing pneumonia (BOOP), using enzyme-linked immunosorbent assay. BALF from all patients was obtained before prednisolone therapy. sFasL levels were relatively increased in IPF patients (p = 0.084), and significantly increased in CVD-IP patients (p < 0.05) and BOOP patients (p < 0.05), compared with control subjects. BALF sFasL levels were elevated in the IPF or CVD-IP subgroups with an indication for prednisolone therapy, compared 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 correlated with the number of total cells or lymphocytes, respectively. The BALF 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 alveolitis in IPF. The elevation of sFasL may be associated with the deterioration of IPF and CVD-IP. The elevation of the BALF sFas level may abrogate the cytotoxicity of FasL in BOOP patients, which may be associated with better prognosis of BOOP, compared with IPF or CVD-IP.

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