title: Birch pollen immunotherapy in mice: inhibition of Th2 inflammation is not sufficient to decrease airway hyper-reactivity.
abstract: BACKGROUND
  Suppression of Th2 cytokine production by allergen-specific Th2 cells is considered to be critical for the suppression of allergic symptoms by subcutaneous immunotherapy. The aim of this study was to develop a mouse model for birch pollen (BP) immunotherapy to elucidate the underlying mechanisms that contribute to the improvement of clinical symptoms.
  
  
  METHODS
  Mice with BP-induced allergic airway inflammation received weekly subcutaneous immunotherapy (SCIT) injections with BP extract (BPE) adsorbed to alum. The effect of an increasing dose of BPE adsorbed to a fixed concentration of alum on the suppression of airway inflammation and airway hyper-responsiveness (AHR) was determined. After 2, 4, 6 or 8 immunotherapy injections, the mice were rechallenged with the same allergen and all hallmarks of allergic asthma were evaluated.
  
  
  RESULTS
  Suppression of the immunological parameters by immunotherapy was dependent on the BPE dose. Two injections were sufficient to suppress IL-4, IL-5, IL-13, IL-10 and IFN-γ production, eosinophil recruitment and peribronchial inflammatory infiltrates. BP-specific immunoglobulins were upregulated, but this was not sufficient to reduce AHR. Eight injections were needed to suppress AHR. The gradual reduction in AHR was inversely associated with the increase of BP IgG2a.
  
  
  CONCLUSIONS
  BP SCIT induces an early suppression of Th2-mediated eosinophilic airway inflammation, but AHR is only effectively reduced after continued SCIT conceivably by allowing IgG2a antibody titres to build up.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Leonie S
authors.initials: LS
authors.lastname: van Rijt
authors.forename: Lara
authors.initials: L
authors.lastname: Gouveia
authors.forename: Adrian
authors.initials: A
authors.lastname: Logiantara
authors.forename: Derya
authors.initials: D
authors.lastname: Canbaz
authors.forename: Dirk-Jan
authors.initials: DJ
authors.lastname: Opstelten
authors.forename: Hanneke P M
authors.initials: HP
authors.lastname: van der Kleij
authors.forename: Ronald
authors.initials: R
authors.lastname: van Ree
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology; D029662:Betula / Q000009:adverse effects*; D016207:Cytokines / Q000096:biosynthesis; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007249:Inflammation / Q000276:immunology; D007279:Injections, Subcutaneous; D051379:Mice; D011058:Pollen / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000628:therapy*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines