IL-13 overexpression predisposes to anaphylaxis following antigen sensitization

Anaphylaxis represents an extreme form of allergic reaction. This acute-pha se component of allergy and asthma is triggered by allergen-induced degranu lation of mast cells following the cross-linking of cell surface-bound, all ergen-specific IgE, resulting in the liberation of inflammatory: mediators and the development of bronchoconstriction. We used IL-13 transgenic mice t o investigate the role of this Th2 cell-derived cytokine in the onset of al lergic disease. Strikingly, IL-13-transgenic mise were highly predisposed t o fatal anaphylaxis following Ag sensitization. This response correlated wi th substantially elevated levels of circulating Ag-specific IgE, mast cell degranulation, and histamine release. Furthermore, allergen exposure also i nduced phenotypic changes typical of asthma, including pulmonary fibrosis, goblet cell hyperplasia, elevated Th2 cytokines, eosinophilia, and airways occluded by mucus and Charcot-Leyden crystals. Expression of IL-4 was not r equired for the induction of IgE-mediated responses. These data represent t he first characterization of a functional role for IL-U-induced IgE in the generation of immediate hypersensitivity reactions and highlight the import ance of IL-13 in the development of the symptoms of atopy. The systemic reg ulation of this response makes these mice an important resource for studyin g atopic responses,