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Prevention of Functional and Pathological Lung Changes in Bleomycin‐Induced Models of Pulmonary Fibrosis with a Pan‐TGF‐b Neutralizing Antibody
Author(s) -
D'Angona Anne Marie,
Finn Patrick,
Gregory Rick,
Philips Lucy,
Lonning Scott,
Andrews Laura,
McVieWylie Alison
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.753.1
Subject(s) - bleomycin , pulmonary fibrosis , idiopathic pulmonary fibrosis , fibrosis , medicine , inflammation , lung , transforming growth factor , antibody , monoclonal antibody , immunology , neutralizing antibody , pathology , chemotherapy
Idiopathic pulmonary fibrosis (IPF) affects 34/1 people per year. Currently there is no cure for IPF, partially because the etiology remains unknown. IPF is believed to develop through three phases: inflammation, alveolar epithelial damage, and fibroblast response resulting in excess matrix. TGF‐b is known to play a critical role in the development of fibrosis in IPF as well as other fibrotic diseases. We have employed the use of a bleomycin‐induced model of pulmonary fibrosis to evaluate a pan‐ TGF‐b neutralizing antibody (1D11) as a potential therapeutic. Although bleomycin treatment induces several pro‐inflammatory and pro‐fibrotic responses, TGF‐b is upregulated and modulation of TGF‐b has been suggested to result in decreased fibrosis. Following bleomycin administration, mice developed fibrosis, which was abrogated by 1D11 treatments. In addition, flexiVent analysis revealed significant changes in functional parameters, which 1D11 treatments improved. In initial studies, direct 1D11 administrations prevented the development of alveolar/perivascular inflammation as well as fibrotic lesions. Furthermore, 1D11 treatments prevented reduction of functional parameters, most notably elastance. These studies have demonstrated functional and histologic improvement with 1D11 and provide support for the utilization of therapeutic TGF‐b neutralizing antibodies for the treatment of IPF.