Aerobic Exercise Attenuated Bleomycin-Induced Lung Fibrosis in Th2-Dominant Mice.
BACKGROUND
The aim of this study was to investigate the effect of aerobic exercise (AE) in reducing bleomycin-induced fibrosis in mice of a Th2-dominant immune background (BALB/c).


METHODS
BALB/c mice were distributed into: sedentary, control (CON), Exercise-only (EX), sedentary, bleomycin-treated (BLEO) and bleomycin-treated+exercised (BLEO+EX); (n = 8/group). Following treadmill adaptation, 15 days following a single, oro-tracheal administration of bleomycin (1.5U/kg), AE was performed 5 days/week, 60min/day for 4 weeks at moderate intensity (60% of maximum velocity reached during a physical test) and assessed for pulmonary inflammation and remodeling, and cytokine levels in bronchoalveolar lavage (BAL).


RESULTS
At 45 days post injury, compared to BLEO, BLEO+EX demonstrated reduced collagen deposition in the airways (p<0.001) and also in the lung parenchyma (p<0.001). In BAL, a decreased number of total leukocytes (p<0.01), eosinophils (p<0.001), lymphocytes (p<0.01), macrophages (p<0.01), and neutrophils (p<0.01), as well as reduced pro-inflammatory cytokines (CXCL-1; p<0.01), (IL-1β; p<0.001), (IL-5; p<0.01), (IL-6; p<0.001), (IL-13; p<0.01) and pro-fibrotic growth factor IGF-1 (p<0.001) were observed. Anti-inflammatory cytokine IL-10 was increased (p<0.001).


CONCLUSIONS
AE attenuated bleomycin-induced collagen deposition, inflammation and cytokines accumulation in the lungs of mice with a predominately Th2-background suggesting that therapeutic AE (15-44 days post injury) attenuates the pro-inflammatory, Th2 immune response and fibrosis in the bleomycin model.
Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE), Rua Vergueiro, 235/249, São Paulo - SP, Brazil.
Adilson Santos
AS
Andrade-Sousa
Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE), Rua Vergueiro, 235/249, São Paulo - SP, Brazil.
Paulo
P
Rogério Pereira
Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE), Rua Vergueiro, 235/249, São Paulo - SP, Brazil.
BreAnne
B
MacKenzie
Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE), Rua Vergueiro, 235/249, São Paulo - SP, Brazil.
Manoel Carneiro
MC
Oliveira-Junior
Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE), Rua Vergueiro, 235/249, São Paulo - SP, Brazil.
Erasmo
E
Assumpção-Neto
Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE), Rua Vergueiro, 235/249, São Paulo - SP, Brazil.
Maysa Alves Rodrigues
MA
Brandão-Rangel
Laboratory of Cellular Biology (LIM 59), School of Medicine, University of São Paulo, Avenida Doutor Arnaldo, 455, Sao Paulo - SP, Brazil.
Nilsa Regina
NR
Damaceno-Rodrigues
Laboratory of Cellular Biology (LIM 59), School of Medicine, University of São Paulo, Avenida Doutor Arnaldo, 455, Sao Paulo - SP, Brazil.
Elia
E
Garcia Caldini
Laboratory of Medical Investigation (LIM 17), School of Medicine, University of São Paulo, Avenida Doutor Arnaldo, 455, Sao Paulo - SP, Brazil.
Ana Paula Pereira
AP
Velosa
Laboratory of Medical Investigation (LIM 17), School of Medicine, University of São Paulo, Avenida Doutor Arnaldo, 455, Sao Paulo - SP, Brazil.
Walcy Rosolia
WR
Teodoro
Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE), Rua Vergueiro, 235/249, São Paulo - SP, Brazil.
Ana Paula
AP
Ligeiro de Oliveira
Department of Pathology, School of Medicine, University of São Paulo, Avenida Doutor Arnaldo, 455, Sao Paulo - SP, Brazil.
Marisa
M
Dolhnikoff
Comprehensive Pneumology Center (CPC), Ludwig Maximilian Universität München and Helmholtz Zentrum München, Max-Lebsche-Platz 31, München, Germany.
Oliver
O
Eickelberg
Laboratory of Pulmonary and Exercise Immunology (LABPEI) and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Nove de Julho University (UNINOVE), Rua Vergueiro, 235/249, São Paulo - SP, Brazil.
Rodolfo Paula
RP
Vieira
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