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Vascular Endothelial Growth Factor Level Correlates With Transforming Growth Factor-ß Isoform Levels in Pleural Effusions^*

^* From the Department of Pulmonary Medicine (Drs. Cheng, Lee, Moyers, Rodriguez and Mr. Rogers), St. Thomas Hospital, and Departments of Medicine (Dr. Light) and Pediatrics (Dr Perkett), Vanderbilt University, Nashville, TN.

Correspondence to: Y. C. Gary Lee, MBChB, Department of Pulmonary Medicine, Saint Thomas Hospital, 4220 Harding Rd, Nashville, TN 37202; e-mail: ycgarylee{at}hotmail.com

Background: Recent studies have demonstrated high levels of vascular endothelial growth factor (VEGF) in exudative pleural effusions and a possible etiologic role. The factors regulating VEGF accumulation in the pleural space are unknown. Transforming growth factor (TGF)-ß is a potent stimulator of VEGF expression in vitro. We hypothesized that TGF-ß induces VEGF production in pleural tissues, and, hence, the pleural fluid VEGF levels should correlate with the levels of TGF-ß in pleural fluid of different etiologies.

Methods: Seventy pleural fluid samples were analyzed. These included 20 malignant, 13 post-coronary artery bypass grafting (CABG), 8 parapneumonic, 11 miscellaneous exudative, and 18 congestive heart failure (CHF) pleural effusions.

Results: Pleural fluid VEGF levels showed good correlation with those of TGF-ß₁ (r = 0.58; p < 0.0001), TGF-ß₂ (r = 0.43; p < 0.001), and lactate dehydrogenase (r = 0.65; p < 0.001). The levels of TGF-ß₁ and TGF-ß₂ also were correlated (r = 0.60; p < 0.0001). The median levels of TGF-ß₁ (2,480 pg/mL) and TGF-ß₂ (266 pg/mL) in the CHF group were significantly lower than those in the malignant (TGF-ß₁, 4,902 pg/mL; TGF-ß₂, 428 pg/mL), post-CABG (TGF-ß₁, 5,456 pg/mL; TGF-ß₂, 377 pg/mL), parapneumonic (TGF-ß₁, 5,024 pg/mL; TGF-ß₂, 464 pg/mL), and miscellaneous exudate groups (TGF-ß₁, 7,690 pg/mL; TGF-ß₂, 369 pg/mL). There was no significant difference in TGF-ß₁ and TGF-ß₂ levels among the four exudate groups.

Conclusions: VEGF levels in pleural effusions are significantly correlated with the levels of TGF-ß₁ and ß₂ isoforms. VEGF, TGF-ß₁, and TGF-ß₂ levels were all higher in exudative effusions than in effusions secondary to CHF.

Key Words: pleural effusions • transforming growth factor-ß • vascular endothelial growth factor

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