Transforming growth factor-beta2 induces pleurodesis significantly faster than talc.
Transforming growth factor-beta2 (TGF-beta2) has recently been shown to produce effective pleurodesis in rabbits. Conventional pleurodesing agents such as talc act by inducing pleural injury, which results in acute inflammation and fibrosis. TGF-beta2 is a profibrotic cytokine capable of producing fibrosis without inducing significant pleural inflammation. We hypothesize that intrapleural administration of TGF-beta2 would (1) produce an effective pleurodesis faster; (2) stimulate more collagen deposition, and (3) induce less inflammation when compared with intrapleural injection of talc. Thirty rabbits were divided into two groups and given either TGF-beta(2) (1.7 microg) or talc slurry (400 mg/kg) via a chest tube. Five rabbits from each group were killed at Days 1, 4, and 7. Gross pleurodesis was graded from 1 (none) to 8 (complete symphysis). The microscopic pleural inflammation and fibrosis were graded from 0 to 4. Pleural thickening and the total area of collagen deposition were compared. Intrapleural injection of TGF-beta2 produced effective pleurodesis within 7 d (median pleurodesis score = 7 at Day 7). At Day 7, TGF-beta2 induced significantly more collagen deposition (19.4 +/- 19.6% versus 4.6 +/- 2.9% of total area of pleura at Day 7), higher pleural fibrosis score (3.0 +/- 1.0 versus 1.8 +/- 0.5), and pleural thickness (286 +/- 191 versus 85 +/- 37 microm) than did talc. There was no difference in the degree of pleural inflammation between the two groups at Day 7 (2.6 +/- 0.9 for TGF-beta2 versus 2.4 +/- 0.6 for talc) or at any other time points. In conclusion, the intrapleural administration of TGF-beta2 produced excellent pleurodesis in rabbits at a rate faster than talc slurry and all other pleurodesing agents investigated before. TGF-beta2 stimulated more collagen deposition without inducing excess inflammation when compared with talc slurry. TGF-beta2 may have advantages over talc slurry in the management of recurrent pleural effusion and pneumothorax.
Gary Lee
Y C
YC
Department of Pulmonary Medicine, St. Thomas Hospital and Vanderbilt University, Nashville, Tennessee 37202, USA.ycgarylee@hotmail.com
Teixeira
L R
LR
Devin
C J
CJ
Vaz
M A
MA
Vargas
F S
FS
Thompson
P J
PJ
Lane
K B
KB
Light
R W
RW
D000818:Animals; D001826:Body Fluids / Q000737:chemistry; D010994:Pleura / Q000473:pathology; D018700:Pleurodesis; D011817:Rabbits; D013627:Talc / Q000008:administration & dosage*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D053781:Transforming Growth Factor beta2
D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D013627:Talc