Monoclonal antibodies anti-TGFβ1 and anti-VEGF inhibit the experimental pleurodesis induced by silver nitrate.

The mechanisms underlying pleural inflammation and pleurodesis are poorly understood. We hypothesized that the cytokines transforming growth factor β (TGFβ1) and vascular endothelial growth factor (VEGF) play a major role in pleurodesis after intrapleural silver nitrate (SN) injection. Forty rabbits received intrapleurally 0.5% SN alone or 0.5% SN + anti-TGFβ1, anti-IL-8, or anti-VEGF. After 28 days, the animals were euthanized and macroscopic pleural adhesions, microscopic pleural fibrosis, and collagen deposition were analyzed for characterization of the degree of pleurodesis (scores 0-4). Scores of pleural adhesions, pleural fibrosis, total collagen, and thin collagen fibers deposition after 28 days were significantly lower for 0.5% SN + anti-TGFβ1 and 0.5% SN + anti-VEGF. Significant correlations were found between macroscopic adhesion and microscopic pleural fibrosis with total collagen and thin collagen fibers. We conclude that both TGFβ1 and VEGF, but not IL-8, mediate the pleural inflammatory response and pleurodesis induced by SN.