Prolonged antigen exposure ameliorates airway inflammation but not remodeling in a mouse model of bronchial asthma.
BACKGROUND
In naive rodents, repeated exposure to aerosolized antigen induces suppression of the Th2 response to the antigen. We hypothesized that more prolonged exposure of established asthma model to antigen aerosols may downregulate asthmatic phenotype.


METHODS
After establishing an ovalbumin (OVA)-induced asthma model, mice were further exposed to OVA (prolonged exposure group) or phosphate-buffered saline (positive controls) 3 days per week for 6 weeks. During week 7, the mice of both groups were finally challenged with OVA.


RESULTS
Prolonged OVA exposure resulted in marked suppression of serum OVA-specific immunoglobulin E (IgE) antibody levels, eosinophilia of the airway, and airway hyperresponsiveness (AHR). However, airway remodeling characterized by goblet cell hyperplasia and airway fibrosis was observed to the same degree in both groups. These effects were accompanied by diminished production of Th2 cytokines such as interleukin-4 (IL-4), IL-5 and IL-13 in bronchoalveolar lavage fluid (BALF) and cultured supernatant of splenocytes. Furthermore, prolonged exposure markedly increased IL-12 levels in BALF.


CONCLUSIONS
Prolonged antigen exposure has inhibitory effects on eosinophilic inflammation, AHR and IgE response to antigen, but not on airway remodeling, presumably via inhibition of Th2 cytokines and increased IL-12 production in the lungs.
Sakai
K
K
Second Department of Internal Medicine, Ehime University, Onsen-gun, Ehime, Japan.
Yokoyama
A
A
Kohno
N
N
Hamada
H
H
Hiwada
K
K
D000818:Animals; D000918:Antibody Specificity; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D005856:Germ-Free Life; D006801:Humans; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology*
D000941:Antigens; D016207:Cytokines; D007073:Immunoglobulin E; D010047:Ovalbumin