ENdothelin-1 in inflammatory and malignant pleural effusions

SESSION TITLE: Pleural EffusionsSESSION TYPE: Original Investigation SlidePRESENTED ON: Tuesday, October 29, 2013 at 02:45 PM - 04:15 PMPURPOSE: Endothelin (ET)-1 can induce epithelial-mesenchymal transition (EMT) and has been shown implicated in tissue fibrosis and cancer metastases. However, the role of ET-1 in inflammatory and malignant pleural effusions has never been investigated. We aimed to determine whether ET-1 has a pathogenic role in exudative effusions and its clinical implication.METHODS: Pleural fluid ET-1 levels were measured in 108 consecutive patients presenting with undiagnosed pleural effusions and the levels were correlated with the etiology of effusions. Treatment outcome and pleural fibrosis, defined as radiological residual pleural thickening (RPT), were assessed at 6-month follow-up. Pleural mesothelial cells (PMCs) harvested from transudative pleural fluids were treated with or without (control) ET-1 (10 nM/ml), and the phenotypic changes and expression of EMT markers were assessed serially for 4 days.RESULTS: Exudative (n = 88) pleural effusions contained significantly higher ET-1 levels than transudative (n = 20) pleural effusions (median 2.55 vs. 1.82 pg/ml, P = 0.007). Median levels of ET-1 in both malignant (n = 32) and tuberculous (n = 36) effusions were significantly higher than those in parapneumonic (n = 20) effusions. The ET-1 levels in pleural fluids varied with different tumor histology. Among tuberculous effusions, 10 patients with RPT had significantly higher effusion ET-1 levels than did those without (P < 0.001). As compared to control, ET-1 time-dependently increased α-smooth muscle actin and decreased E-cadherin expression, and induced mesenchymal transformation of PMCs.CONCLUSIONS: ET-1 levels are raised in the majority of exudative effusions and are associated with tuberculous pleural fibrosis, implying a role for ET-1 in the pathogenesis of pleural effusion and fibrosis. The EMT effect of ET-1 on PMCs may indicate a biological activity of ET-1 on pleural tissue.CLINICAL IMPLICATIONS: Further studies are warranted to determine the clinical value of effusion ET-1 as a prognostic factor and a surrogate indicator of fibrogenesis in exudative pleural effusions.DISCLOSURE: The following authors have nothing to disclose: Chi-Li Chung, Wei-Lin Chen, Shih-Hsin Hsiao, George HsiaoNo Product/Research Disclosure Information