Aerobic Exercise Attenuated Bleomycin-Induced Lung Fibrosis in Th2-Dominant Mice

Abstract

IntroductionThe 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).MethodsBALB/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).ResultsAt 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).ConclusionAE 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.

Exercise training ameliorates bleomycin‐induced epithelial mesenchymal transition and lung fibrosis through restoration of H2S synthesis

“…In the past few years, several retrospective, prospective and randomized controlled trails have demonstrated that IPF patients in short‐term exercise programs experience significant improvements in some outcomes such as six‐minute walk scores, body composition and quality of life . In consistent with these clinical trials, previous and our own basic science studies showed that moderate‐intensity exercise intervention significantly attenuated bleomycin‐induced lung fibrosis in mice, as evidenced by the improvement of damaged lung structure and decreases in collagen deposition, pulmonary contents of hydroxyproline and type I collagen, thus further supporting the protective effect of exercise training against pulmonary fibrosis.…”

“…To date, few studies have examined the intimate mechanisms involved in the beneficial effects of exercise training against pulmonary fibrosis. Recently, Vieira's group demonstrates that exercise training attenuates bleomycin‐induced inflammation, cytokine accumulation and fibrosis in the lung tissue, and these effects may be mediated by increased IL‐10 production, decreased Th2 immune response and inhibition of aberrant 5‐hydroxytryptamine (5‐HT) and Akt signalling . EMT, a process by which epithelial cells undergo phenotypic transition to more motile mesenchymal cells, has been highlighted as a potential contributor to cellular transdifferentiation during fibrotic disorders .…”

Exercise Improves Lung Inflammation, but Not Lung Remodeling and Mechanics in a Model of Bleomycin-Induced Lung Fibrosis

“…Our findings here demonstrate that, even though the exercise training was not able to alter the collagen deposition in the parenchyma or even some key pulmonary mechanic parameters, the aerobic exercise training putatively reduced the recruitment of immune system cells, the release of proinflammatory mediators/cytokines both in the lung and blood, and increased the IL-10 expression by lung macrophages of mice submitted to an experimental model of bleomycin-induced lung fibrosis. It is worth to mention that the findings of Pereira et al [ 8 ] and Andrade-Souza et al [ 21 ] corroborate our results, since these authors demonstrated that the exercise training promoted a significant reduction of immune cells number (and also proinflammatory cytokines) in the BAL of mice presenting pulmonary fibrosis compared to nonexercised control. However, the novelty of our study is settled on the benefits of the aerobic exercise training, here proposed as a “nonpharmacological intervention,” starting from the very beginning of lung aggression induced by bleomycin administration, while in the study from Pereira et al [ 8 ] and Andrade-Souza [ 21 ], the exercise training started after two weeks of bleomycin administration.…”

Aerobic Exercise Protects from Pseudomonas aeruginosa-Induced Pneumonia in Elderly Mice

“…In concordance with many of our group’s previous studies, in this study, exercise induced IL-10 expression in the BAL as well as parenchymal and epithelial lung cells, and remained elevated for at least 24 h following inoculation [17, 18, 20, 37, 43, 49]. Thus, the anti-inflammatory cytokine IL-10 is not only significantly elevated by exercise alone, levels also persist following a variety of lung injury models, including allergic asthma [17, 18, 20, 37, 49] and lung fibrosis induced by bleomycin [50, 51], COPD [52, 53], and LPS [43, 54]. Conversely, expression of the master inflammatory regulator NF-κB in lung parenchyma was attenuated by exercise.…”