Increased expression of tumor necrosis factor receptors in cryptogenic organizing pneumonia

Abstract

Background: TNF receptors (TNFR1 and TNFR2) and Fas belong to the system of apoptosis-signalling receptor molecules and may play a role in the pathogenesis of interstitial lung disease. Patients with cryptogenic organizing pneumonia (COP) usually respond well to corticosteroids, in contrast to those with idiopathic pulmonary fibrosis (IPF). This may be due to the different pathogenesis.

Methods: The expression of TNFR1, TNFR2 and Fas on bronchoalveolar lavage (BAL) macrophages and lymphocytes was analysed in 9 patients with COP, 10 with IPF and 12 controls. The production of soluble TNFR1, 2 and TNF-α by alveolar macrophages was measured by ELISA.

Results: TNFR1 and Fas expression on alveolar macrophages was significantly higher in COP than in controls and IPF. The expression of TNFR2 on alveolar macrophages was also increased in COP compared to controls. The expression of TNFR2 and Fas on lymphocytes was significantly higher in COP than in IPF and controls. In addition, the expression of TNFR1, TNFR2 and Fas on BAL cells correlated positively with BAL lymphocytes (p < 0.05 or p < 0.01). The production of sTNFR1 and 2 and TNF-α by macrophages in vitro was significantly increased in patients with COP compared to IPF and controls, spontaneously or with LPS stimulation (p < 0.05 or p < 0.01).There was a positive correlation between the spontaneous production of sTNFR2 and TNF-α (r = 0.494, p < 0.01).

Conclusions: This study showed an increased expression of TNF receptors and Fas on BAL cells in COP that may be indicative of the local inflammatory activity in the lung. The biologic effects of this expression needs further investigation.