IL-13 fusion cytotoxin ameliorates chronic fungal-induced allergic airway disease in mice

IL-13 has emerged as a major contributor to allergic and asthmatic response s, and as such it represents an attractive target in these diseases. In thi s study, IL-13-responsive cells in the lung were targeted via the intranasa l administration of IL-13-PE38QQR (IL-13-PE), comprised of human IL-13 and a derivative of Pseudomonas exotoxin, to Aspergillus fumigatus-sensitized m ice challenged with A. fumigatus spores, or conidia. Mice received 50, 100, or 200 ng of IL-13-PE or diluent alone (i.e., control group) on alternate days from day 14 to day 28 after the conidia challenge. The control group o f mice exhibited significant airway hyperreactivity, goblet cell hyperplasi a, and peribronchial fibrosis at day 28 after conidia. Although the two low er doses of IL-13-PE had limited therapeutic effects in mice with fungal-in duced allergic airway disease, the highest dose of IL-13-PE tested signific antly reduced all features of airway disease compared with the control grou p. Whole lung mRNA expression of IL-4R alpha and IL-13R alpha1 was markedly reduced, whereas bronchoalveolar lavage and whole lung levels of IFN-gamma were significantly elevated in mice treated with 200 ng of IL-13-PE compar ed with the control group. This study demonstrates that a therapy designed to target IL-13-responsive cells in the lung ameliorates established fungal -induced allergic airway disease in mice.