Vascular endothelial growth factor (VEGF) in inflammatory and malignant pleural effusions

Background-Investigation and management of pleural effusions is an importan t clinical problem yet the pathogenesis of pleural fluid accumulation is po orly understood. Vascular endothelial growth factor (VEGF) is a potent indu cer of capillary permeability that is produced by both malignant and inflam matory cells. A study was undertaken to determine whether VEGF has a potent ial pathogenic role in the development of pleural effusions and whether VEG F receptors are present on human pleural mesothelial cells. Methods-Normal and inflamed pleura were examined immunohistochemically for the presence of FLT-1 (the fms-like tyrosine kinase receptor of VEGF). VEGF levels were measured by ELISA in 78 consecutive patients presenting with u ndiagnosed unilateral pleural effusions and the levels were correlated with the aetiology of the effusions. Results-immunohistochemical staining of normal and diseased pleura demonstr ated the presence of the FLT-1 VEGF receptor on human mesothelial cells. Me dian VEGF levels were 2500 pg/ml in the malignant group and 305 pg/ml in th e non-malignant group (median difference 1397.5 pg/ml (95% CI 851 to 2693), p<0.005). Median VEGF levels varied according to tumour histology. VEGF le vels were also significantly raised compared with transudates (median 36.5 pg/ mi) in empyema (4651 pg/ml (95% CI 833 to 10 000), p<0.001) and parainf ectious effusions (360 pg/ml (95% CI 46 to 597), p<0.005). Conclusions-This first report of VEGF receptors on pleural mesothelial cell s has indicated a potential mechanism for the biological activity of VEGF o n pleural tissue. VEGF levels are raised in the majority of exudative effus ions, implying a pathogenic role for this molecule in the development of pl eural effusions.