title: Inhibition of IL-4/IL-13 does not enhance the efficacy of allergen immunotherapy in murine allergic airway inflammation.
abstract: BACKGROUND
  Successful allergen-specific immunotherapy (SIT) is associated with reduced Th2 cytokine production and the induction of IL-10-producing regulatory T cells. To improve treatment efficacy, we investigated the impact of an IL-4/IL-13 inhibitor during SIT.
  
  
  METHODS
  BALB/c mice were sensitized intranasally with ovalbumin (OVA) for 4 weeks. Subsequently, they were subjected to intranasal SIT, with OVA being administered at doses increasing from 1 mug to 1 mg over 3 weeks with or without an IL-4/IL-13 inhibitor. Serum OVA-specific antibodies were measured and bronchoalveolar lavage (BAL) fluids were checked for airway eosinophilia. Subsequently, lung tissue was examined histologically for inflammatory infiltrates. Cytokines were detected in BAL fluids and spleen cell cultures. Furthermore, CD4 CD25 double-positive spleen T cells were checked for intracellular IL-10 production by flow cytometry.
  
  
  RESULTS
  OVA sensitization resulted in persistent IgE synthesis and an eosinophil-rich allergic airway inflammation combined with increased IL-4 and IL-5 levels. Therefore, intranasal SIT could efficiently reverse the allergic phenotype. This was associated with decreased IL-4 and IL-5 levels, and increased IL-10 levels in BAL fluids as well as increased amounts of IL-10-producing CD25+ regulatory T cells. However, mice treated with the IL-4/IL-13 inhibitor during SIT did not produce significantly different results .
  
  
  CONCLUSIONS
  The use of an IL-4/IL-13 inhibitor as an adjuvant for SIT did not enhance anti-allergic effects. Thus, the observed reversal of Th2 responses during SIT may not be the keystone for successful therapy, but rather other factors, e.g. IL-10-producing regulatory T cells, may be crucial.
authors.affiliation: Department of Dermatology, University of Wurzburg, Wurzburg, Germany.
authors.forename: Tea
authors.initials: T
authors.lastname: Gogishvili
authors.forename: Christian
authors.initials: C
authors.lastname: Hahn
authors.forename: Julia
authors.initials: J
authors.lastname: Meinhard
authors.forename: Andreas
authors.initials: A
authors.lastname: Hohaus
authors.forename: Klaus
authors.initials: K
authors.lastname: Erb
authors.forename: Walter
authors.initials: W
authors.lastname: Sebald
authors.forename: Eva B
authors.initials: EB
authors.lastname: Bröcker
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Grunewald
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D003888:Desensitization, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000517:prevention & control*; D007249:Inflammation / Q000517:prevention & control*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D018793:Interleukin-13 / Q000037:antagonists & inhibitors*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D018793:Interleukin-13; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10; D015847:Interleukin-4; D010047:Ovalbumin