The benefits of moderate aerobic physical exercise for allergic asthma are well-known, particularly that of the anti-inflammatory effect that occurs by reducing Th2 responses and lung remodeling. However, the mechanisms of this immunoregulation are still under investigation. In this study, we investigated the possible immunoregulatory mechanisms of lung inflammation induced by moderate aerobic exercise in an experimental asthma model. BALB/c mice were distributed into Control, Exercise (EX), OVA, and OEX groups. OVA and OEX groups were sensitized with ovalbumin (OVA) on days 0, 14, 21, 28, and 42 and were challenged with OVA aerosol three times a week from days 21 to 51. The EX and OEX groups underwent moderate aerobic physical exercise from days 21 to 51 (5 d/w, 1 h/d). The mice were euthanized on day 52. We evaluated pulmonary cytokine production, serum immunoglobulin levels, and the inflammatory cell profile in lung and mediastinal lymph nodes. OVA mice showed increased expression of IL-4, IL-6, IL-10, and TGF-β and decreased macrophage type 2 (M2) recruitment. Physical exercise did not affect the increased antibody production of IgG2a, IgG1, or IgE induced by OVA. Of note, physical exercise alone markedly increased production of anti-inflammatory cytokines such as IL-10 and TGF-β. Physical exercise in OVA-mice also increased the recruitment of M2 in the lungs, as well as the influx and activation of regulatory T cells (Tregs) and CD4 and CD8 lymphocytes. In the draining lymph nodes, it was also observed that physical exercise increased the activation of CD4 T cells, regardless of the presence of OVA. Notably, physical exercise decreased common dendritic cells' (cDCs; pro-inflammatory) expression of co-stimulatory molecules such as CD80, CD86, and ICOSL in the draining lymph nodes, as well as increased ICOSL in plasmacytoid dendritic cells (pDCs; anti-inflammatory). Together, these findings show that physical exercise modulates pulmonary allergic inflammation by increasing Treg and M2 recruitment, as well as pDCs activation, which leads to an increase in anti-inflammatory cytokines and a decrease in pro-inflammatory cells and mediators.
Asthma is an allergic lung disease and, when associated to cigarette smoke exposition, some patients show controversial signs about lung function and other inflammatory mediators. Epidemiologic and experimental studies have shown both increasing and decreasing inflammation in lungs of subjects with asthma and exposed to cigarette smoke. Therefore, in this study, we analyzed how cigarette smoke affects pro-inflammatory and anti-inflammatory mediators in a murine model of allergic pulmonary inflammation. We sensitized Balb/c mice to ovalbumin (OVA) with two intraperitoneal injections. After sensitization, the animals were exposed to cigarette smoke twice a day, 30 min per exposition, for 12 consecutive days. In order to drive the cell to the lungs, four aerosol challenges were performed every 48 h with the same allergen of sensitization. OVA sensitization and challenge developed pulmonary Th2 characteristic response with increased airway responsiveness, remodeling, increased levels of IgE, interleukin (IL)-4, and IL-13. Cigarette smoke, unexpectedly, reduced the levels of IL-4 and IL-13 and simultaneously decreased anti-inflammatory cytokines as IL-10 and transforming growth factor (TGF)-β in sensitized and challenged animals. OVA combined with cigarette smoke exposition decreased the number of eosinophils in bronchoalveolar lavage and increased the number of neutrophils in lung. The combination of cigarette smoke and lung allergy increased recruitment of lymphoid dendritic cells (DCs) into lymph nodes, which may be the leading cause to an increase in number and activation of CD8+ T cells in lungs. In addition, lung allergy and cigarette smoke exposure decreased an important regulatory subtype of DC such as plasmacytoid DC as well as its activation by expression of CD86, PDL2, and ICOSL, and it was sufficient to decrease T regs influx and anti-inflammatory cytokines release such as IL-10 and TGF-β but not enough to diminish the structural changes. In conclusion, we observed, in this model, that OVA sensitization and challenge combined with cigarette smoke exposure leads to mischaracterization of the Th2 response of asthma by decreasing the number of eosinophils, IL-4, and IL-13 and increasing number of neutrophils, which is related to the increased number of CD8ɑ+ DCs and CD8+ T cells as well as reduction of the regulatory cells and its released cytokines.
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