IL-13 overexpression predisposes to anaphylaxis following antigen sensitization.
Anaphylaxis represents an extreme form of allergic reaction. This acute-phase component of allergy and asthma is triggered by allergen-induced degranulation of mast cells following the cross-linking of cell surface-bound, allergen-specific IgE, resulting in the liberation of inflammatory mediators and the development of bronchoconstriction. We used IL-13 transgenic mice to investigate the role of this Th2 cell-derived cytokine in the onset of allergic disease. Strikingly, IL-13-transgenic mice were highly predisposed to fatal anaphylaxis following Ag sensitization. This response correlated with substantially elevated levels of circulating Ag-specific IgE, mast cell degranulation, and histamine release. Furthermore, allergen exposure also induced 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 required for the induction of IgE-mediated responses. These data represent the first characterization of a functional role for IL-13-induced IgE in the generation of immediate hypersensitivity reactions and highlight the importance of IL-13 in the development of the symptoms of atopy. The systemic regulation of this response makes these mice an important resource for studying atopic responses.
Fallon
P G
PG
Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Emson
C L
CL
Smith
P
P
McKenzie
A N
AN
D000707:Anaphylaxis / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage* / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D020022:Genetic Predisposition to Disease; D007114:Immunization; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008174:Lung Diseases, Parasitic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000953:Antigens, Protozoan; D016207:Cytokines; D018793:Interleukin-13