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Published ahead of print on March 16, 2006, doi:10.1165/rcmb.2005-0293OC

Am. J. Respir. Cell Mol. Biol., Volume 35, Number 2, August 2006, 211-219

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Submitted on July 28, 2005
Revised on March 14, 2006

Role of Local Pulmonary Interferon Gamma Expression in Murine Allergic Airway Inflammation

Markus Koch1*, Martin Witzenrath2, Christine Reuter1, Marion Herma1, Hartwig Schutte2, Norbert Suttorp2, Helen Collins3, and Stefan H.E. Kaufmann1

1 Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany, 2 Department of Internal Medicine, Charite Humboldt-University, Berlin, Germany, 3 Division of Life Sciences, Kings College London, London, United Kingdom

* To whom correspondence should be addressed. E-mail: koch{at}mpiib-berlin.mpg.de.

Generalized underrepresentation of interferon-gamma (IFN-{gamma}) has been implicated in the development of allergic asthma. However, the role of local IFN-{gamma} in the lung during the development of this disease has not been completely elucidated. We studied the influence of local pulmonary IFN-{gamma} expression on the development of allergen-induced lung inflammation. To restrict our analysis to IFN-{gamma} expression in the lung and to exclude influences of systemic IFN-{gamma} production, we generated a transgenic mouse line with a targeted deletion of the IFN-{gamma} gene and constitutive, lung-specific IFN-{gamma} expression (CC10-IFN-{gamma}-tg-IFN-{gamma}-KO mice), and compared allergen-induced airway inflammation in these mice with that of wild-type and IFN-{gamma}-KO mice on the C57BL/6 background. Cytokine quantification in lungs of mice with allergic airway inflammation revealed that pulmonary IFN-{gamma} expression increased expression of IL-5 and IL-13. Consistent with this observation, eosinophilia in bronchoalveolar lavage of CC10-IFN-{gamma}-tg-IFN-{gamma}-KO mice was profoundly increased, indicating that this critical component of asthma is enhanced by local IFN-{gamma} expression. In contrast, airway hyperresponsiveness (AHR) and anti OVA-IgE serum levels were reduced by local IFN-{gamma} expression. Together, our results demonstrate pleiotropic action of constitutive IFN-{gamma} expression in the lung and question the therapeutic value of IFN-{gamma} in allergic asthma.




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