Avaliação dos mecanismos imunomoduladores da ouabaína no modelo experimental de asma induzida por ovalbumina

Abstract

Allergic inflammatory disorders such as TH2 hi asthma can be treated in their late phase with corticosteroids, which end up promoting an improvement in the chronic inflammatory condition that settles in the airways. Ouabain, a cardiotonic steroid with immunomodulatory properties, is able to regulate histamine release by mast cells in simple allergic processes, and to attenuate ovalbumin-induced allergic airway inflammation (OVA). These findings reinforce the physiological role played by ouabain during allergic inflammatory responses, showing evidence of the physiological and pharmacological modulating potential of this substance in asthmatic processes. Therefore, the objective of this study was to evaluate the effect of treatment with ouabain on cellular, endothelial and histological parameters characteristic of the TH2 hi asthma model. For this, we used an experimental model of OVA-induced asthma with a duration of 12 weeks. Female Balb/c mice were primed with OVA on days 0 and 14 and from days 21 to 84 for three consecutive days per week were challenged with aerosolized OVA. Treatment with ouabain and the standard drug budesonide occurred one hour before each challenge and on the 85th day of the protocol, biological material was collected. The animals with asthma treated with ouabain showed a reduction (p<0.05) in the migration of total cells and individually of eosinophils, macrophages and lymphocytes in the bronchoalveolar fluid lavage (BALF); serum levels of total and OVA-specific IgE; cytokine levels in BALF (IL-33, TSLP, IL-4, IL-1β, TGF-β and TNF-α); inflammation and overproduction of mucus in the lungs; of bronchial hyperreactivity and lung tissue remodeling. Additionally, treatment with ouabain reduced the frequency of p-p38 MAPK activation in lymphocytes in BALF. Thus, the results obtained in this study suggest that ouabain as an immunomodulatory cardiotonic steroid is able to reduce the main characteristics that determine the allergic asthmatic endotype, known as TH2 hi asthma.