Abstract
Malignant pleural effusion (MPE) is a frequent and dismal clinical event signaling incurability and severely compromised quality of life. Smoking fuels mutagenesis, initiation and progression of lung cancer. Nicotine, the major alcaloid of tobacco, favors proliferation and survival of lung cancer and malignant mesothelioma cells. Whether cigarette smoke (CS) affects pleural malignancies and MPE remains unknown. Pro-inflammatory and pro-angiogenic smoking properties favor this possibility, since inflammation and angiogenesis are critical aspects of MPE pathogenesis. In this study we sought to determine the role of cigarette smoke in MPE using a mesothelioma-induced MPE syngeneic model. C57BL/6 mice were exposed upon 4 weeks CS (3R4F University of Kentucky, USA). At the 2nd week of smoking the mice were subjected to intrapleural injection of AE17 cells. Control animals were exposed to room air. CS-exposed group presented significantly (p=0.002) larger pleural effusions (1018±87.7μl) compared to control (697±88.8μl). Tumor size was similar between groups. Interestingly, CS-exposed mice exhibited higher numbers of tumor promoting, M2-polarized macrophages. We also investigated the effect of cigarette smoke in naive, tumor intact, animals. We witnessed increased pleural cellularity, pleural neutrophil and pro-tumor T-regulatory cell accumulation in cigarette smoke-exposed mice. Conclusively, cigarette-smoke promotes MPE formation by enhancing tumor-associated inflammation. Pro-Inflammatory properties of CS in naïve mice further denotes its possible role in benign and/or malignant pleural effusion.
- Copyright ©ERS 2015