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Intrapleural Injection of Transforming Growth Factor-ß Antibody Inhibits Pleural Fibrosis in Empyema^*

^* From the Section of Pulmonary and Critical Care Medicine, Department of Medicine (Drs. Kunz and Sasse, Mr. Nguyen), and Department of Pathology (Drs. Jadus and Kukes), Long Beach Veterans Affairs Healthcare System and University of California, Irvine; and Maternal-Child HIV Research Center (Dr. Kramer) University of Southern California, Los Angeles, CA.

Correspondence to: Scott A. Sasse, MD, FCCP, Section of Pulmonary and Critical Care Medicine, Long Beach Veterans Affairs Healthcare System, 5901 East Seventh St (11–111P), Long Beach, CA 90822; e-mail: scott.sasse{at}med.va.gov

Study objectives: Transforming growth factor (TGF)-ß is a cytokine that has been demonstrated to be an important modulator of inflammation and angiogenesis, as well as a potent stimulator of pleural fluid production and fibrosis. We previously demonstrated that rising levels of pleural fluid TGF-ß₁ correlate with pleural fibrosis in experimental empyema in rabbits. In this study, our hypothesis is that neutralization of TGF-ß with an intrapleural injection of a monoclonal antibody to TGF-ß will decrease pleural fibrosis in empyema.

Design: Prospective, randomized, blinded study.

Setting: Animal research laboratory.

Subjects: Nineteen rabbits.

Interventions: An empyema was induced in 19 rabbits by intrapleural injection of Pasteurella multocida. A panspecific monoclonal antibody to TGF-ß was injected into the pleural space on 2 subsequent concurrent days in nine rabbits. Ten rabbits received intrapleural injections of bacteria alone and served as controls. All animals were then killed on day 6. Immunohistochemistry, using the antibody to TGF-ß, was performed on pleural tissue specimens from the control rabbits.

Measurements and results: Immunohistochemistry revealed localization of TGF-ß to macrophages in the exudative material and the visceral pleura. After injection of the antibody to TGF-ß, the amount of purulent, exudative material in the pleural space of the nine experimental animals was markedly decreased at autopsy on day 6, relative to control animals. All markers of empyema and pleural fibrosis were also significantly decreased in the rabbits receiving intrapleural anti–TGF-ß.

Conclusions: TGF-ß localizes to macrophages in experimental empyema. Early intrapleural injection of an antibody to TGF-ß inhibits empyema formation and significantly decreases pleural fibrosis in experimental empyema.

Key Words: cytokines • empyema • fibrosis • pleural

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