BACKGROUNDAerobic exercise can improve symptoms, reduce airway inflammation, and even ameliorate airway remodeling in asthmatic animals and patients. However, previous studies have focused mainly on the effect of aerobic exercise on steroid-sensitive asthma (SSA). The goals of this study were to determine the effect of low-intensity aerobic exercise training on airway hyperresponsiveness, inflammation, and remodeling in a rat model of steroid-resistant asthma (SRA) and to identify the potential mechanisms underlying these effects.

METHODSEndotoxin-free ovalbumin with or without lipopolysaccharide were applied to establish rat models of SRA and SSA, respectively. Airway hyperresponsiveness, inflammation, remodeling, expression of interleukin (IL)-25, IL-33, thymic stromal lymphopoietin (TSLP), high mobility group box-1 (HMGB1), and IL-17 in bronchoalveolar lavage fluid (BALF), and the role of dexamethasone (DXM) were compared between these two asthmatic rat models. The effect of low-intensity aerobic exercise training and anti-HMGB1 treatment on airway hyperresponsiveness, inflammation, and remodeling in SRA rats also was evaluated.

RESULTSSRA rats developed neutrophil-dominated airway inflammation ((29.5±4.1)% of the total cell numbers in BALF), whereas SSA rats developed eosinophil-dominated airway inflammation ((24.0±6.1)% of the total cell numbers in BALF). Compared with SSA rats, SRA rats had more severe airway hyperresponsiveness, lower levels of IL-25 ((33.6±10.3) vs. (104.8±24.9) pg/ml), IL-33 ((87.5±25.0) vs. (226.6±40.7) pg/ml), and TSLP ((1 933.2±899.5) vs. (7 224.0±992.1) pg/ml), and higher levels of HMGB1 ((21.2±4.5) vs. (5.4±1.6) ng/ml) and IL-17 ((780.5±261.7) vs. (291.4±76.4) pg/ml) in BALF (all P < 0.05). However, there was no significant difference in goblet cell hyperplasia, subepithelial collagen thickness, and airway smooth muscle remodeling between the two groups. Compared with control SSA rats, airway hyperresponsiveness, inflammation, and remodeling in SRA rats were less sensitive to DXM treatment. Anti-HMGB1 treatment attenuated airway hyperresponsiveness, inflammation, and remodeling in SRA rats to a certain extent and was accompanied by lower levels of IL-17 ((369.2±126.7) vs. (780.5±261.7) pg/ml in control SRA rats) in BALF (P < 0.05). Low-intensity aerobic exercise training decreased the expression of both HMGB1 ((14.1±2.9) vs. (21.2±4.5) ng/ml in control SRA rats) and IL-17 ((545.3±148.6) vs. (780.5±261.7) pg/ml in control SRA rats) in BALF (all P < 0.05) and was accompanied by improved airway hyperresponsiveness, inflammation, and remodeling in SRA rats (all P < 0.05).

CONCLUSIONSLow-intensity aerobic exercise training attenuated airway hyperresponsiveness, inflammation, and remodeling in a rat model of SRA. Decreased HMGB1 and IL-17 levels in BALF by aerobic exercise training at least partly contributed to the improvements of SRA.