Intrapleural injection of transforming growth factor-beta antibody inhibits pleural fibrosis in empyema.
OBJECTIVE
Transforming growth factor (TGF)-beta 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-beta(1) correlate with pleural fibrosis in experimental empyema in rabbits. In this study, our hypothesis is that neutralization of TGF-beta with an intrapleural injection of a monoclonal antibody to TGF-beta will decrease pleural fibrosis in empyema.


METHODS
Prospective, randomized, blinded study.


METHODS
Animal research laboratory.


METHODS
Nineteen rabbits.


METHODS
An empyema was induced in 19 rabbits by intrapleural injection of Pasteurella multocida. A panspecific monoclonal antibody to TGF-beta 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-beta, was performed on pleural tissue specimens from the control rabbits.


RESULTS
Immunohistochemistry revealed localization of TGF-beta to macrophages in the exudative material and the visceral pleura. After injection of the antibody to TGF-beta, 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-beta.


CONCLUSIONS
TGF-beta localizes to macrophages in experimental empyema. Early intrapleural injection of an antibody to TGF-beta inhibits empyema formation and significantly decreases pleural fibrosis in experimental empyema.
Kunz
Craig R
CR
Section of Pulmonary and Critical Care Medicine, Long Beach Veterans Affairs Healthcare System, 5901 East Seventh St (11-111P), Long Beach, CA 90822, USA.
Jadus
Martin R
MR
Kukes
Gary D
GD
Kramer
Françoise
F
Nguyen
Vu N
VN
Sasse
Scott A
SA
D000818:Animals; D016724:Empyema, Pleural / Q000150:complications*; D005355:Fibrosis; D015552:Injections, Intralesional; D008297:Male; D010994:Pleura / Q000473:pathology*; D010995:Pleural Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011446:Prospective Studies; D011817:Rabbits; D011897:Random Allocation; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
D016212:Transforming Growth Factor beta