[The therapeutic effect of TGF-beta monoclonal antibody to bleomycin-induced pulmonary fibrosis in rats].
OBJECTIVE
Transforming growth factor-beta (TGF-beta) plays an important role in the pathogenesis of interstitial lung fibrosis. It can stimulate indirectly the mitosis of lung fibroblasts (LFb) as well as the synthesis and disposition of extracellular matrix. The purpose of this study was to evaluate the effects of TGF-beta monoclonal antibody on bleomycin-induced interstitial pulmonary fibrosis.


METHODS
The effect of TGF-beta monoclonal antibody to bleomycin-induced pulmonary fibrosis in rat was studied either in vivo or in vitro. The proliferation of lung fibroblasts was studied by measuring the incorporation rate of 3H-TdR. Northern hybridization was used to detect mRNA level of procollagen A1 (I) and procollagen A1 (II) in cultured LFbs and lung tissue.


RESULTS
The results showed that the incubation supernatant of alveolar macrophages from rats with pulmonary fibrosis had the ability to stimulate fibroblast proliferation as well as their procollagen expression. The monoclonal antibody could inhibit the proliferation of LFbs in a concentration-dependent manner. The highest concentration, 100 micrograms/ml, of TGF-beta antibody could inhibit incorporation rate from 1749 +/- 322 of the fibrosis group to only 833 +/- 277 (P < 0.01). The mRNA level of procollagen I and II was decreased by 44% and 28% respectively after the antibody treatment. In vivo, procollagen I and II mRNA level were decreased by 40% and 12% after the administration of TGF-beta antibody though it could only slightly alleviate the extent of fibrosis and alveolitis in lung tissue.


CONCLUSIONS
TGF-beta is a key factor stimulating the proliferation and collagen synthesis. TGF-beta antibody can partially neutralize its action. This may suggest that the antibody might become a new therapeutic choice for pulmonary fibrosis in the future.
Li
J
J
Department of Pulmonary Medicine, First Clinical College, Beijing Medical University.
He
B
B
Weng
B
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001761:Bleomycin; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D008297:Male; D011347:Procollagen / Q000096:biosynthesis* / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000276:immunology*
D000911:Antibodies, Monoclonal; D011347:Procollagen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D001761:Bleomycin