Role of Local Pulmonary IFN- Expression in Murine Allergic Airway Inflammation

Generalized underrepresentation of IFNhas been implicated in the development of allergic asthma. However, the role of local IFNin the lung during the development of this disease has not been completely elucidated. We studied the influence of local pulmonary IFNexpression on the development of allergen-induced lung inflammation. To restrict our analysis to IFNexpression in the lung and to exclude influences of systemic IFNproduction, we generated a transgenic mouse line with a targeted deletion of the IFNgene and constitutive, lung-specific IFNexpression (Clara cell 10 [CC10]–IFN–tg–IFN–KO mice), and compared allergen-induced airway inflammation in these mice with that of wild-type and IFN– KO mice on the C57BL/6 background. Cytokine quantification in lungs of mice with allergic airway inflammation revealed that pulmonary IFNexpression increased expression of IL-5 and IL-13. Consistent with this observation, eosinophilia in bronchoalveolar lavage of CC10–IFN–tg–IFN–KO mice was profoundly increased, indicating that this critical component of asthma is enhanced by local IFNexpression. In contrast, airway hyperresponsiveness and anti-ovalbumin-IgE serum levels were reduced by local IFNexpression. Together, our results demonstrate pleiotropic action of constitutive IFNexpression in the lung, and question the therapeutic value of IFNin allergic asthma. Local expression of IFNin the lung increases markers of allergic airway inflammation, but decreases airway hyperresponsiveness in a murine model of allergicasthma