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Pleurodesis Is Inhibited by Anti-Vascular Endothelial Growth Factor Antibody^*

^* From the Department of Respiratory and Critical Care Medicine (Dr. Guo), the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ROC; Department of Critical Care and Pulmonary Services (Dr. Kalomenidis), Athens Medical School, Evangelismos Hospital, Athens, Greece; Mouse Pathology and Immunostaining Core Facility (Ms. Parman), Vanderbilt University Medical Center, Nashville, TN; and Department of Pulmonary Medicine (Drs. Hawthorne, Lane, and Light), St. Thomas Hospital and Vanderbilt University, Nashville, TN.

Correspondence to: Richard W. Light, MD, FCCP, Department of Pulmonary Medicine, St. Thomas Hospital, 4220 Harding Rd, Nashville, TN 37205; e-mail: rlight98{at}yahoo.com

Study objectives: The intrapleural injection of transforming growth factor (TGF)-ß₂ produces pleurodesis in rabbits associated with large pleural effusions. This study investigated whether anti-vascular endothelial growth factor (VEGF) antibody has any effect on the fluid production or the pleurodesis induced by TGF-ß₂.

Interventions and measurements: Three groups of seven New Zealand white rabbits were administered TGF-ß₂ 5.0 µg intrapleurally. Two groups received anti-VEGF antibody (10 mg/kg and 25 mg/kg) IV 24 h before TGF-ß₂ injection, and the third group received no antibody. The rabbits were killed at 2 weeks, and the macroscopic pleurodesis score was determined. The degree of pleural angiogenesis was assessed by immunohistochemical staining for factor VIII.

Results: The administration of anti-VEGF antibodies had no significant effect on the pleural fluid volume or the characteristics of the fluid. The mean pleurodesis score of the seven rabbits in the control group (7.71 ± 0.76) was significantly (p < 0.05) higher than that for seven rabbits in the low-dose treatment group (4.43 ± 2.37) and the seven rabbits in the high-dose treatment group (4.57 ± 2.36) [± ]. The percentage of pleural tissue demonstrating angiogenesis in the control group (4.87 ± 0.43%) was significantly (p < 0.05) higher than that for the low-dose (2.94 ± 0.68%) or high-dose (2.67 ± 0.64%) antibody groups. When all rabbits were considered, there was a highly significant correlation between the pleural vascular density scores and the pleurodesis scores (r = 0.84, p < 0.01).

Conclusion: VEGF and angiogenesis appear to play a pivotal role in the production of a pleurodesis.

Key Words: angiogenesis • pleura • pleurodesis • transforming growth factor-ß₂ • vascular endothelial growth factor

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