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Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109; and
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
IL-13 has emerged as a major contributor to allergic and asthmatic
responses, and as such it represents an attractive target in these
diseases. In this study, IL-13-responsive cells in the lung were
targeted via the intranasal administration of IL-13-PE38QQR (IL-13-PE),
comprised of human IL-13 and a derivative of Pseudomonas
exotoxin, to Aspergillus fumigatus-sensitized mice
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 of mice exhibited significant airway
hyperreactivity, goblet cell hyperplasia, and peribronchial fibrosis at
day 28 after conidia. Although the two lower doses of IL-13-PE had
limited therapeutic effects in mice with fungal-induced allergic airway
disease, the highest dose of IL-13-PE tested significantly reduced all
features of airway disease compared with the control group. Whole lung
mRNA expression of IL-4R
and IL-13R1 was markedly reduced,
whereas bronchoalveolar lavage and whole lung levels of IFN-
were
significantly elevated in mice treated with 200 ng of IL-13-PE compared
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.
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