Azithromycin reduces pulmonary fibrosis in a bleomycin mouse model.
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.
Wuyts
W A
WA
Laboratory of Pneumology, Katholieke Universiteit Leuven and University Hospitals Leuven, Leuven, Belgium. wim.wuyts@uzleuven.be
Willems
S
S
Vos
R
R
Vanaudenaerde
B M
BM
De Vleeschauwer
S I
SI
Rinaldi
M
M
Vanhooren
H M
HM
Geudens
N
N
Verleden
S E
SE
Demedts
M G
MG
Thomeer
M
M
Verbeken
E K
EK
Verleden
G M
GM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017963:Azithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D001761:Bleomycin; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007113:Immunity, Innate / Q000187:drug effects*; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012129:Respiratory Function Tests
D000900:Anti-Bacterial Agents; D015415:Biomarkers; D016207:Cytokines; D001761:Bleomycin; D017963:Azithromycin