title: Mucosal tolerance as therapy of type I allergy: intranasal application of recombinant Bet v 1, the major birch pollen allergen, leads to the suppression of allergic immune responses and airway inflammation in sensitized mice.
abstract: BACKGROUND
  Several studies have demonstrated that mucosal administration of soluble antigens can prevent the onset or reduce the severity of certain autoimmune diseases or allergies. Few studies exist showing the efficacy of mucosal tolerance for therapy of such diseases.
  
  
  OBJECTIVE
  The aim of the present study was to modulate an allergic immune response by intranasal antigen administration in an already sensitized organism.
  
  
  METHODS
  A murine model of allergic asthma to birch pollen (BP) and its major allergen Bet v 1 was utilized. Sensitized mice were intranasally treated with recombinant (r)Bet v 1 in different concentrations and at different intervals. On the day the mice were killed, blood and bronchoalveolar lavage fluids were taken and immediate type I skin tests were performed. T cell proliferation and cytokine production (interleukin (IL)-5, interferon (IFN)-gamma) were measured in spleen and lung cell cultures.
  
  
  RESULTS
  Mucosal treatment with rBet v 1 (3 x 50 microg in 4 day intervals) led to a reduction of type I skin reactions, suppressed immunoglobulin (Ig)G1/IgE antibody levels and markedly decreased IL-5 and IFN-gamma production in vitro in spleen and lung cell cultures. Moreover, lung inflammation (i.e. eosinophilia and IL-5 levels in bronchoalveolar lavage fluids) was significantly suppressed by the treatment.
  
  
  CONCLUSIONS
  Our results demonstrate that intranasal treatment with rBet v 1 reduced systemic allergic immune responses as well as airway inflammation in BP-sensitized mice. We therefore suggest that mucosal tolerance induction with recombinant allergens could be a promising concept for the therapy of allergic diseases.
authors: Department of Pathophysiology, University of Vienna, Austria.
authors: B
authors: B
authors: Winkler
authors: K
authors: K
authors: Baier
authors: S
authors: S
authors: Wagner
authors: A
authors: A
authors: Repa
authors: H G
authors: HG
authors: Eichler
authors: O
authors: O
authors: Scheiner
authors: D
authors: D
authors: Kraft
authors: U
authors: U
authors: Wiedermann
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000917:Antibody Formation; D052179:Antigens, Plant; D002455:Cell Division; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006969:Hypersensitivity, Immediate / Q000150:complications / Q000276:immunology* / Q000628:therapy*; D007108:Immune Tolerance; D007114:Immunization; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation / Q000209:etiology / Q000628:therapy; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010940:Plant Proteins / Q000627:therapeutic use*; D011058:Pollen; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D020545:Respiratory Mucosa / Q000276:immunology*; D012140:Respiratory Tract Diseases / Q000209:etiology* / Q000628:therapy*; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014197:Trees
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; D010940:Plant Proteins; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula