Characteristic features of allergic airway inflammation in a murine model of infantile asthma.
BACKGROUND
The pathophysiology of infantile asthma may differ from that in older children or in adults, partly because of the different immune response depending upon maturation. In adult mice, the sensitizing dose of antigen is known to be critical to the polarized development of helper T cell subsets and allergic airway inflammation. We wanted to know the characteristics of allergic airway inflammation of infantile asthma by developing a murine model.


METHODS
BALB/C mice at different stages of maturation (juvenile: 3 days after birth; adult: 8 weeks of age) were sensitized with 10 or 1,000 microg ovalbumin (OVA) or vehicle. The animals were then challenged with aerosolized OVA or saline once a day during 6 consecutive days. After the final challenge, bronchial hyperresponsiveness (BHR), bronchoalveolar lavage fluid (BALF), histological changes in the airways and immunological status were examined.


RESULTS
In both juvenile and adult animals, sensitization with 10 microg OVA induced the T helper 2 response (elevated IL-4 and decreased IFN-gamma levels). BHR, airway eosinophilia, the inflammatory cell infiltration, goblet cell metaplasia (GCM), and IgE antibody production were more prominent in animals given this dose than 1,000 microg OVA. Among these responses, GCM as well as BALF IL-4, and BHR were comparable between juvenile and adult animals, whereas other parameters were lower in juvenile animals, especially in those given 1,000 microg OVA.


CONCLUSIONS
GCM and, consequently, airway mucus hypersecretion may be an important component of allergic airway inflammation in infantile asthma.
Ohki
Yasushi
Y
Department of Pediatrics and Developmental Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Tokuyama
Kenichi
K
Mayuzumi
Hiroo
H
Sato
Akira
A
Koyama
Harumi
H
Takizawa
Takumi
T
Arakawa
Hirokazu
H
Mochizuki
Hiroyuki
H
Morikawa
Akihiro
A
D000367:Age Factors; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004802:Eosinophilia / Q000276:immunology / Q000503:physiopathology; D020397:Goblet Cells / Q000473:pathology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008679:Metaplasia / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D007073:Immunoglobulin E; D010047:Ovalbumin