title: Upon prolonged allergen exposure IL-4 and IL-4Ralpha knockout mice produce specific IgE leading to anaphylaxis.
abstract: BACKGROUND
  IL-4 and IL-13 are key regulators in atopic disorders and both signal through the receptor chain IL-4Ralpha. IL-4 and IL-13 are also the only cytokines known to induce class switching to IgE. We sought to compare allergen-specific IgE responses and allergic reactivity of wild-type (wt) mice with IL-4-/- and IL-4Ralpha-/- mice, which lack both IL-4 and IL-13 functions.
  
  
  METHODS
  BALB/c wt, IL-4-/- and IL-4Ralpha-/- mice were immunized with ovalbumin intranasally or intraperitoneally and specific antibody titers were measured by ELISA. Bronchoalveolar lavage fluids and lung tissue were analyzed cytologically and histologically. Allergic reactivity was determined by active cutaneous anaphylaxis and anaphylactic shock.
  
  
  RESULTS
  wt mice immunized intranasally or intraperitoneally showed high titers of specific IgE 3 and 6 weeks after primary sensitization, resulting in cutaneous anaphylaxis and anaphylactic shock upon challenge. Intranasal sensitization resulted in airway eosinophilia and goblet cell metaplasia. In contrast, IL-4-/- and IL-4Ralpha-/- mice showed no specific IgE after 3 weeks, but produced high titers after 6 weeks. At this time cutaneous anaphylaxis and anaphylactic shock could be induced as in wt mice, but lung pathology was absent.
  
  
  CONCLUSIONS
  We conclude that upon long-term allergen exposure, alternative switch mechanisms independent of IL-4 and IL-4Ralpha may induce IgE but not asthma-like lung pathology. This may be relevant for the development of allergic disease, since long-term allergen exposure is a frequent condition during allergic sensitization.
authors.affiliation: Klinik und Poliklinik für Haut- und Gechlechtskrankheiten, Universität Würzburg, Josef-Schneider-Strasse 2, D-97080 Würzburg, Germany. grunewald-s.derma@mail.uni-wuerzburg.de
authors.forename: S M
authors.initials: SM
authors.lastname: Grunewald
authors.forename: M
authors.initials: M
authors.lastname: Teufel
authors.forename: K
authors.initials: K
authors.lastname: Erb
authors.forename: A
authors.initials: A
authors.lastname: Nelde
authors.forename: M
authors.initials: M
authors.lastname: Mohrs
authors.forename: F
authors.initials: F
authors.lastname: Brombacher
authors.forename: E B
authors.initials: EB
authors.lastname: Bröcker
authors.forename: W
authors.initials: W
authors.lastname: Sebald
authors.forename: A
authors.initials: A
authors.lastname: Duschl
mesh_terms: D000485:Allergens / Q000276:immunology*; D000707:Anaphylaxis / Q000209:etiology*; D000818:Animals; D004802:Eosinophilia / Q000209:etiology; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D018793:Interleukin-13 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology*; D008679:Metaplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D019948:Receptors, Interleukin-4 / Q000502:physiology*
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin