Modulation of pulmonary allergic responses by mucosal cytokine-gene transfer

Recent clinical and experimental animal studies have provided evidence for a pivotal role of T lymphocytes and Th2 cytokines in the development of allergic inflammatory responses and airway hyperreactivity. These studies suggest also that the Th2 cytokine-associated inflammatory responses are potential targets of developing novel and effective therapies. Using a novel gene-transfer approach, we investigated the role of a Th2-inhibitory cytokine, IFN-?, in the regulation of antigen (Ag)-induced lung inflammatory response and airway hyperreactivity by transfer of the IFN-? gene into mouse lung mucosal cells. Our results showed that mice receiving the IFN-? gene demonstrate a lower degree of Ag- and Th2 cell-induced airway hyperresponsiveness and a reduced eosinophilia in the lung. These results provided evidence that the instillation of the IFN-y gene into the lung is effective in modulating the allergic inflammation and bronchial hyperreactivity in an experimental animal model.