BACKGROUND: Allergic asthma strongly correlates with airway inflammation caused by cytokines secreted by allergen-specific type-2 T helper (Th2) cells, but the immunologic regulation of cell function is yet to be acquired. Further, IL-10 has been found to exert both antiinflammatory and immunoregulatory activities. This study aimed to elucidate the therapeutic effects of IL-10 administration via adenovirus-mediated gene delivery on airway inflammation in the ovalbumin (OVA)-induced murine model of asthma. METHODS: BALB/c mice were sensitized by intraperitoneal injections with OVA and challenged by nebulized OVA. The sensitized mice were given an intratracheal delivery of adenoviral vector expressing the murine IL-10 gene (AdIL-10), or mock adenoviral vector 4 days before the inhalation challenge of the OVA. Inflammatory parameters, such as the development of airway hyper-responsiveness (AHR), bronchial lavage fluid eosinophils, and chemokines were assayed. RESULTS: Intratracheal administration of AdIL-10 could efficiently inhibit antigen-induced AHR and significantly decrease the number of eosinophils and neutrophils in the bronchoalveolar lavage fluid of OVA-sensitized and challenged mice during the effector phase. CONCLUSIONS: Our data showed that the intratracheal transfer of the IL-10 gene could affect the recruitment of inflammatory cells during the challenge phase in a way that would result in the inhibition of airway inflammation. These findings suggest that the development of an immunoregulatory strategy based on IL-10 might shed light on more effective treatment. Copyright 2006 John Wiley & Sons, Ltd.
BACKGROUND:Allergic asthma strongly correlates with airway inflammation caused by cytokines secreted by allergen-specific type-2 T helper (Th2) cells, but the immunologic regulation of cell function is yet to be acquired. Further, IL-10 has been found to exert both antiinflammatory and immunoregulatory activities. This study aimed to elucidate the therapeutic effects of IL-10 administration via adenovirus-mediated gene delivery on airway inflammation in the ovalbumin (OVA)-induced murine model of asthma. METHODS: BALB/c mice were sensitized by intraperitoneal injections with OVA and challenged by nebulized OVA. The sensitized mice were given an intratracheal delivery of adenoviral vector expressing the murineIL-10 gene (AdIL-10), or mock adenoviral vector 4 days before the inhalation challenge of the OVA. Inflammatory parameters, such as the development of airway hyper-responsiveness (AHR), bronchial lavage fluid eosinophils, and chemokines were assayed. RESULTS: Intratracheal administration of AdIL-10 could efficiently inhibit antigen-induced AHR and significantly decrease the number of eosinophils and neutrophils in the bronchoalveolar lavage fluid of OVA-sensitized and challenged mice during the effector phase. CONCLUSIONS: Our data showed that the intratracheal transfer of the IL-10 gene could affect the recruitment of inflammatory cells during the challenge phase in a way that would result in the inhibition of airway inflammation. These findings suggest that the development of an immunoregulatory strategy based on IL-10 might shed light on more effective treatment. Copyright 2006 John Wiley & Sons, Ltd.