Hierarchical suppression of asthma-like responses by mucosal tolerance.
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).
Keller
Alexandre C
AC
Department of Immunology, Biomedical Science Institute, University of São Paulo, Brazil.
Mucida
Daniel
D
Gomes
Eliane
E
Faquim-Mauro
Eliana
E
Faria
Ana Maria Caetano
AM
Rodriguez
Dunia
D
Russo
Momtchilo
M
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
D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin