Acute exercise decreases airway inflammation, but not responsiveness, in an allergic asthma model

Abstract

Previous studies have suggested that the asthmatic responses of airway inflammation, remodeling, and hyperresponsiveness (AHR) are interrelated; in this study, we used exercise to examine the nature of this interrelationship. Mice were sensitized and challenged with ovalbumin (OVA); mice were then exercised via running on a motorized treadmill at a moderate intensity. Data indicate that, within the lungs of OVA-treated mice, exercise attenuated the production of inflammatory mediators, including chemokines KC, RANTES, and MCP-1 and IL-12p40/p80. Coordinately, OVA-treated and exercised mice displayed decreases in leukocyte infiltration, including eosinophils, as compared with sedentary controls. Results also show that a single bout of exercise significantly decreased phosphorylation of the NFkappaB p65 subunit, which regulates the gene expression of a wide variety of inflammatory mediators. In addition, OVA-treated and exercised mice exhibited decreases in the levels of Th2-derived cytokines IL-5 and IL-13 and the prostaglandin PGE(2), as compared with sedentary controls. In contrast, results show that a single bout of exercise had no effect on AHR in OVA-treated mice challenged with increasing doses of aerosolized methacholine (0-50 mg/ml) as compared with sedentary mice. Exercise also had no effect on epithelial cell hypertrophy, mucus production, or airway wall thickening in OVA-treated mice as compared with sedentary controls. These findings suggest that a single bout of aerobic exercise at a moderate intensity attenuates airway inflammation but not AHR or airway remodeling in OVA-treated mice. The implication of these findings for the interrelationship between airway inflammation, airway remodeling, and AHR is discussed.

Figure 1.

One bout of aerobic exercise at a moderate intensity decreased chemokine production in ovalbumin (OVA)-treated mice. Twenty-four hours after protocol completion, bronchoalveolar lavage (BAL) was performed; resulting lavagates were analyzed for changes in (A) KC, (B) RANTES, (C) MCP-1, and (D) IL-12p40/p80 via multiplex assay. Results are reported as pg/ml of respective protein (^†P < 0.006 as compared with saline-treated, sedentary mice; *P < 0.04 as compared with OVA-treated, sedentary mice; n = 4–8 mice per group). Open bars, sedentary mice; solid bars, exercised mice.

Figure 2.

A single bout of moderate intensity aerobic exercise decreased leukocyte infiltration in OVA-treated mice. Twenty-four hours after protocol completion, BAL was performed and resulting lavagates were analyzed for changes in total cells and eosinophils. Results were are reported as changes in cell number (^†P < 0.03 as compared with saline-treated, sedentary mice; *P < 0.04 as compared with OVA-treated, sedentary mice; ND, none detected; n = 4 mice per group). Open bars, sedentary mice; solid bars, exercised mice.

Figure 3.

A single bout of moderate-intensity aerobic exercise p65 phosphorylation in the lungs of OVA-treated mice. 24 h post protocol completion, lungs were harvested, lysed and prepared for analyses of total and phosphorylated p65 levels via p65-specific enzyme-linked immunosorbent assay (ELISA); phosphorylated p65 levels were normalized against total p65 levels. Results are reported as fold difference in phospho-NFκB-p65 levels as compared with saline-treated, sedentary controls (^†P < 0.05 as compared with saline-treated, sedentary mice; *P < 0.05 as compared with OVA-treated, sedentary mice; n = 4 mice per group). Open bars, sedentary mice; solid bars, exercised mice.

Figure 4.

One bout of moderate-intensity aerobic exercise decreased Th2-derived cytokine production in OVA-treated mice. Twenty-four hours after protocol completion, BAL was performed and resulting lavagates were analyzed for changes in (A) IL-5 and (B) IL-13 via multiplex assay. Results are reported as pg/ml of respective protein (^†P < 0.001 as compared with saline-treated, sedentary mice; *P < 0.001 as compared with OVA-treated, sedentary mice; ND, none detected; n = 4–8 mice per group). Open bars, sedentary mice; solid bars, exercised mice.

Figure 5.

A single bout of moderate-intensity aerobic exercise had no effect on AHR in OVA-treated mice. Forty-eight hours after protocol completion, mice were assessed for changes in AHR upon methacholine challenge at increasing concentrations via mechanical ventilation. Results are reported as measurements of total lung resistance (R, cm H₂O/ml/s; ^†P < 0.04 as compared with saline-treated, sedentary mice; n = 4–8 mice per group). Open squares, sedentary, saline-treated mice; solid circles, exercised, saline-treated mice; open triangles, sedentary, OVA-treated mice; solid triangles, exercised, OVA-treated mice.

Figure 6.

A single bout of moderate-intensity aerobic exercise had no effect on airway remodeling in OVA-treated mice. Twenty-four hours after protocol completion, lung tissues were harvested, PASH stained, and prepared for analysis of hypertrophy/hyperplasia of the mucosal epithelium, goblet cell and mucin production, and overall airway wall thickening. Representative micrographs of five to six separate experiments are shown: (A) saline-treated, sedentary; (B) saline-treated, exercised; (C) OVA-treated, sedentary; (D) OVA-treated, exercised (*airway lumen; ×10 magnification [inset, ×40]).

Figure 7.

One bout of moderate-intensity aerobic exercise decreased PGE₂ production in OVA-treated mice. Twenty-four hours after protocol completion, BAL was performed and resulting lavagates were analyzed for changes in PGE₂ content via ELISA. Results are reported as ng/ml (^†P < 0.001 as compared with saline-treated, sedentary mice; *P < 0.01, as compared with OVA-treated, sedentary; n = 6–8 mice per group). Open bars, sedentary mice; solid bars, exercised mice.