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

Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin; Department of Internal Medicine, Charite, Humboldt-University, Berlin, Germany; and Division of Life Sciences, Kings College London, London, United Kingdom

Correspondence and requests for reprints should be addressed to Markus Koch, Department of Immunology, Max-Planck-Institute for Infection Biology, Campus Charité Mitte, Schumannstrasse 21/22, 10117 Berlin, Germany. E-mail: koch{at}mpiib-berlin.mpg.de

Generalized underrepresentation of IFN- has been implicated in the development of allergic asthma. However, the role of local IFN- in the lung during the development of this disease has not been completely elucidated. We studied the influence of local pulmonary IFN- expression on the development of allergen-induced lung inflammation. To restrict our analysis to IFN- expression in the lung and to exclude influences of systemic IFN- production, we generated a transgenic mouse line with a targeted deletion of the IFN- gene and constitutive, lung-specific IFN- expression (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 IFN- expression 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 IFN- expression. In contrast, airway hyperresponsiveness and anti-ovalbumin-IgE serum levels were reduced by local IFN- expression. Together, our results demonstrate pleiotropic action of constitutive IFN- expression in the lung, and question the therapeutic value of IFN- in allergic asthma. Local expression of IFN- in the lung increases markers of allergic airway inflammation, but decreases airway hyperresponsiveness in a murine model of allergic-asthma

Key Words: airway hyperresponsiveness • asthma • eosinophilia • IFN- • transgenic mice

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