Vasoactive mediators (VEGF and TNF-alpha) in patients with malignant and tuberculous pleural effusions.

Abstract

Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific mitogen that promotes angiogenesis, vascular hyperpermeability, and vasodilatation by autocrine mechanisms involving nitric oxide (NO). This study was undertaken to determine the potential role of VEGF in the pathogenesis of pleural effusions, and its relationship with tumour necrosis factor (TNF)-alpha and NO in the pleural fluid and serum of patients with tuberculous and malignant pleural effusions. Pleural fluid and serum (SE) VEGF, TNF-alpha and NO levels were measured in 30 patients with exudative pleural effusion (15 with malignancies and 15 with tuberculosis). Control pleural fluid was obtained from 10 patients with transudative pleural effusion due to congestive heart failure and control serum samples were obtained from 10 healthy individuals. VEGF and TNF-alpha were measured by enzyme-linked immunosorbent assay and NO by a colorimetric method. Pleural biopsy, cytology or microbiological methods were used to make the final diagnosis. In patients with exudative pleural effusions, the mean pleural fluid and serum VEGF levels and their ratios (P < 0.0001 for all) and TNF-alpha levels (P < 0.01, P < 0.0001 and P < 0.05) were significantly elevated compared to those with transudative pleural effusion. In malignant effusions, pleural fluid and serum VEGF levels were significantly elevated (P < 0.001 and P < 0.0001) while pleural fluid, and serum levels and their ratios of TNF-alpha (P < 0.001, P < 0.01 and P < 0.05) were significantly lower than those in tuberculosis. NO levels did not distinguish between tuberculous and malignant effusions. In patients with malignant pleural effusions, levels of VEGF were significantly higher, while levels of TNF-alpha were significantly lower, than in patients with tuberculous effusions. In malignant pleural effusions, the elevated pleural fluid levels of VEGF and TNF-alpha are noteworthy. Our data support the hypothesis that blockade of VEGF, might benefit cancer patients with recurrent ascites or pleural fluid accumulation.