1. Azithromycin reduces pulmonary fibrosis in a bleomycin mouse model.
- Author
-
Wuyts WA, Willems S, Vos R, Vanaudenaerde BM, De Vleeschauwer SI, Rinaldi M, Vanhooren HM, Geudens N, Verleden SE, Demedts MG, Thomeer M, Verbeken EK, and Verleden GM
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Azithromycin pharmacology, Biomarkers analysis, Bleomycin, Body Weight, Bronchoalveolar Lavage Fluid chemistry, Bronchoalveolar Lavage Fluid cytology, Cytokines analysis, Disease Models, Animal, Drug Evaluation, Preclinical, Female, Idiopathic Pulmonary Fibrosis etiology, Idiopathic Pulmonary Fibrosis pathology, Leukocyte Count, Lung pathology, Mice, Mice, Inbred C57BL, Respiratory Function Tests, Anti-Bacterial Agents therapeutic use, Azithromycin therapeutic use, CD4-Positive T-Lymphocytes drug effects, Idiopathic Pulmonary Fibrosis drug therapy, Immunity, Innate drug effects
- Abstract
Idiopathic pulmonary fibrosis (IPF) is a devastating disease without proper treatment. Despite intensive research, the exact underlying pathogenesis remains elusive. It is regarded as a continuous injury, resulting in inflammation, infiltration, and proliferation of fibroblasts and extracellular matrix deposition, leading to an irreversible restrictive lung function deterioration and death. In this study the effect of azithromycin, a macrolide antibiotic on bleomycin-induced pulmonary fibrosis was investigated. C57BL/6 mice were intratracheally instilled with bleomycin (0.5 mg/kg) or saline. In the bleomycin group, half of the animals received azithromycin every other day from day 1 on. Bronchoalveolar lavage and histology were performed at days 7 and 35, and pulmonary function tests on day 35. At day 35, fibrotic lesions (spindle cell proliferation/collagen I deposition) were paralleled by a restrictive lung function pattern. Alterations were found in neutrophils and macrophages (innate immunity) and in T(H)2, T(H)17, and Treg cytokines (adaptive immunity). Azithromycin significantly reduced both fibrosis and the restrictive lung function pattern. This study demonstrated a beneficial effect of azithromycin on bleomycin-induced pulmonary fibrosis. A possible mechanism could be a modulation of both innate immunity and adaptive immunity. These findings might suggest a potential role for azithromycin in the treatment of IPF.
- Published
- 2010
- Full Text
- View/download PDF