Systemic and local interferon gamma gene delivery to the lungs for treatment of allergen-induced airway hyperresponsiveness in mice

Allergen-induced airway hyperresponsiveness, an animal model of asthma in h umans, may respond to immunotherapy with Th1 cytokines, For example, local administration of recombinant IL-12 or IFN-gamma, or intratracheal delivery of the genes for these cytokines, has been shown to reduce the severity of allergen-induced airway hyperresponsiveness (AHR) in rodent models, We rea soned that systemic cytokine gene delivery to the lungs by intravenous inje ction of lipid-DNA complexes might also be an effective approach to treatme nt of allergen-induced AHR. Therefore, the effects of either systemic or lo cal pulmonary IFN-gamma gene delivery were evaluated in mice with allergen- induced AHR, The effects of treatment on AHR, airway eosinophilia and cytok ine production, and serum IgE concentrations were evaluated in mice that we re first sensitized to ovalbumin and then subjected to aerosol ovalbumin ch allenge. Intravenous IFN-gamma gene delivery significantly inhibited develo pment of AHR and airway eosinophilia and decreased serum IgE levels, compar ed with control mice or mice treated with noncoding DNA, Intratracheal IFN- gamma gene delivery also significantly inhibited AHR and airway eosinophili a, but did not affect serum IgE levels. Treatment with recombinant IFN-gamm a was much less effective than IFN-gamma gene delivery by either route. We conclude that either systemic or local pulmonary delivery of a Th1 cytokine gene such as IFN-gamma may be an effective approach for treatment of aller gen-induced asthma.