Papel da Ouabaína na inflamação alérgica pulmonar: aspectos fenotípicos e funcionais

Abstract

Ouabain (OUA), a potent Na+/K+ ATPase inhibitor, was identified as an endogenous substance present in human plasma. It was shown that OUA is able to interfere in several aspects of the immune system and inflammation, but the effect of this substance in allergic lung inflammation had not been previously investigated. Lower airways inflammation process is characterized by cell migration and bronchial hyperresponsiveness, as a result of sensitization by protein antigens such as ovalbumin (OVA). Aim: Evaluate the effect of ouabain on the model of allergic pulmonary inflammation induced by OVA. Methods: BALB/c mice (n = 6) were sensitized and challenged with OVA and pretreated intraperitoneally (ip) with OUA (0.56 mg/kg) two days before the sensitization and one hour before them, or dexamethasone (2 mg/kg) subcutaneously 1 hour before to each challenge. Allergic inflammation parameters, such as cell migration, and production of cytokines in bronchoalveolar lavage fluid (BALF), mucus production and pulmonary histopathologic remodeling, and IgE quantitation were analyzed posteriorly. Results: Ouabain reduced (60%) BALF cells as a reflex of polymorphonuclear leukocyte inhibition and T CD3+ lymphocytes, as well as it reduced the production of Th2 profile cytokines, IL-4 and IL-13. Furthermore, ouabain also reduced histopathologic parameters of inflammation, such as hyperplasia of goblet cells and with consequent mucus decrease, besides it reduced OVA-specific IgE titer. Conclusion: These results suggests that OUA presents anti-inflammatory effect on pulmonary allergic inflammation, modulating Th2 phenotype parameters.