Azithromycin Attenuates Respiratory Syncytial Virus Bronchiolitis through Changing Activation of Treg and Th17 and Related Cytokines

Abstract

Background: Bronchiolitis, which is primarily caused by respiratory syncytial virus (RSV) infecting the lower respiratory tract, is a problematic condition for the health of infants and young children. This study aims to provide deeper insight into RSV-induced bronchiolitis and potential effective treatments. Methods: Sprague Dawley (SD) rats were randomly divided into three groups: rats without RSV infection (NC), rats with RSV infection (RSV) and rats with RSV infection and azithromycin treatment (RSV-A). The changes of lung pathology were evaluated by observing lung sections stained with hematoxylin and eosin (H&E) through the microscope and inflammatory cells in bronchoalveolar lavage fluid (BALF). In addition, fluorescence-activated cell sorting (FACS) and flow cytometry were used to measure percentage of the regulatory T-cell (Treg) and T helper 17 cell (Th17). Treg/Th17-related cytokines were measured by enzyme-linked immunosorbent assays (ELISA), and their related transcription factors were examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Results: Lung tissues from rats in the RSV group presented symptoms of inflammatory cell infiltration, wide alveolar septa, pulmonary interstitial hyperemia and edema, and bronchial collapse and deformation. Additionally, total white blood cells (WBCs), and the percentages of eosinophils, lymphocytes and neutrophils in all WBCs were increased in the RSV group. The percentage of Treg cells, and the levels of transforming growth factor beta (Tgf-β), Interleukin (Il)-17, Il-10, forkhead box P3 (Foxp3) in the RSV group were decreased. In contrast, the percentage of Th17 cells, the concentrations of Il-17 and Il-23, and the retinoic acid-related orphan receptor (RoR)γt in the RSV group were increased. All these changes caused by RSV infection could be attenuated by azithromycin treatment. Conclusion: RSV-induced bronchiolitis could cause severe histological changes and inflammation, which was associated with a decrease in Treg cells and related cytokines and an increase in Th17 cells and related cytokines. Azithromycin could effectively attenuate those symptoms by restoring Treg cells, Th17 cells, and their related cytokines. These findings suggest that azithromycin has the potential to treat RSV-induced bronchiolitis in humans.