title: Inhibition of the IL-4/IL-13 receptor system prevents allergic sensitization without affecting established allergy in a mouse model for allergic asthma.
abstract: BACKGROUND
  IL-4 and IL-13 are considered as key regulators for the development of atopic disease.
  
  
  OBJECTIVE
  This study addresses the therapeutic potential of an IL-4/IL-13 inhibitor on the basis of a mutated IL-4 variant (Q116D, Y119D) during allergic sensitization and in established disease in a murine asthma model with persistent airway pathologic condition.
  
  
  METHODS
  BALB/c mice were sensitized with ovalbumin intranasally. Mice were treated with the IL-4/IL-13 inhibitor during the sensitization phase or alternatively after ovalbumin allergy was established. Specific antibodies were measured, and histologic lung sections were examined for goblet cell metaplasia. In addition, bronchoalveolar lavages were performed and checked for airway eosinophilia, IL-5 levels, and the number of IL-4 secreting CD4(+) T cells. Furthermore, airway responsiveness to inhaled methacholine was assessed.
  
  
  RESULTS
  The inhibition of the IL-4/IL-13 system during allergic sensitization resulted in a dose-dependent reduction of ovalbumin-specific IgEs and inhibition of airway eosinophilia together with decreased IL-5 levels and decreased numbers of IL-4 secreting CD4(+) T cells. Moreover, goblet cell metaplasia and airway responsiveness to methacholine could be reduced significantly by the IL-4/IL-13 inhibitor. However, the inhibition of the IL-4/IL-13 system at various time points after allergy was established showed only little effect on all measured allergic parameters.
  
  
  CONCLUSIONS
  Although the inhibition of the IL-4/IL-13 system can efficiently prevent the development of the allergic phenotype, these cytokines seem to play a minor role in established allergy. This is relevant for estimating the therapeutic effects of IL-4/IL-13 inhibitors in patients with allergic asthma.
authors.affiliation: Klinik und Poliklinik für Haut- und Geschlechtskrankheiten, Universität Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hahn
authors.forename: Martin
authors.initials: M
authors.lastname: Teufel
authors.forename: Udo
authors.initials: U
authors.lastname: Herz
authors.forename: Harald
authors.initials: H
authors.lastname: Renz
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Erb
authors.forename: Gisela
authors.initials: G
authors.lastname: Wohlleben
authors.forename: Eva B
authors.initials: EB
authors.lastname: Bröcker
authors.forename: Albert
authors.initials: A
authors.lastname: Duschl
authors.forename: Walter
authors.initials: W
authors.lastname: Sebald
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Grunewald
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010047:Ovalbumin / Q000276:immunology; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000037:antagonists & inhibitors*; D013997:Time Factors
chemical_list: D000485:Allergens; C508183:Il13ra1 protein, mouse; D053661:Interleukin-13 Receptor alpha1 Subunit; D015848:Interleukin-5; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin