title: Hierarchical suppression of asthma-like responses by mucosal tolerance.
abstract: BACKGROUND
  Mucosal tolerance can be induced by oral or nasal administration of soluble proteins and results in the suppression of cellular and/or humoral immune responses to the specific antigen.
  
  
  OBJECTIVE
  To compare the effect of oral or nasal ovalbumin administration before, during or after immunization on the development of cellular and humoral immune responses by using a murine asthma model.
  
  
  METHODS
  To induce lung allergic inflammation, animals were immunized twice with ovalbumin/aluminum hydroxide gel and challenged twice with ovalbumin. To induce tolerance, BALB/c mice received ovalbumin by the oral or nasal routes for 3 consecutive days. The ovalbumin administration was initiated before (day -7), during (day 0), or after immunization (day 7).
  
  
  RESULTS
  Airway eosinophilia, airway hyperreactivity, mucus hypersecretion, and cytokine production were suppressed when oral or nasal ovalbumin administration was initiated before immunization. Oral but not nasal ovalbumin exposure suppressed ovalbumin-specific nonanaphylactic IgG(1) antibodies, whereas both routes suppressed the production of anaphylactic IgG(1) and IgE antibodies. Mucosal ovalbumin administration at day 0 inhibited all T(H)2-mediated allergic parameters but not nonanaphylactic IgG(1) antibodies. Finally, ovalbumin exposure 7 days after immunization was still effective in suppressing lung allergy but not ovalbumin-specific anaphylactic IgG(1) and IgE antibodies.
  
  
  CONCLUSIONS
  We show that the effectiveness of mucosal tolerance depends on route and time and presents a hierarchical pattern of suppression in the following order: lung allergic responses > anaphylactic antibodies > ovalbumin-specific IgG(1).
authors.affiliation: Department of Immunology, Biomedical Science Institute, University of São Paulo, Brazil.
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Keller
authors.forename: Daniel
authors.initials: D
authors.lastname: Mucida
authors.forename: Eliane
authors.initials: E
authors.lastname: Gomes
authors.forename: Eliana
authors.initials: E
authors.lastname: Faquim-Mauro
authors.forename: Ana Maria Caetano
authors.initials: AM
authors.lastname: Faria
authors.forename: Dunia
authors.initials: D
authors.lastname: Rodriguez
authors.forename: Momtchilo
authors.initials: M
authors.lastname: Russo
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D016535:Bronchial Hyperreactivity / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage; D011657:Pulmonary Eosinophilia / Q000276:immunology; D013997:Time Factors
chemical_list: D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin