| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
Clinical features of asthma in infants differ from those in older patients. This may have been partly caused by age-dependent differences in the immune response. Thus, we examined the characteristic features of allergic airway inflammation of infantile asthma by developing a murine model. In adult mice, the sensitizing dose of antigen is known to be critical to the development of polarized helper T cell subsets, and of allergic airway inflammation. Thus, we sensitized animals of different stages of maturation with different doses of antigen, in order to observe a maturational changes in airway responses under different immunological conditions. Juvenile or adult BALB/C mice were sensitized with low or high doses of ovalbumin (OVA) or vehicle. Animals were, then, challenged with aerosolized OVA or normal saline once a day during 6 consecutive days. After the final challenge, bronchial hyperresponsiveness (BHR), the number of cells in bronchoalveolar lavage fluid (BALF), histological analysis of airways, and serum OVA-specific antibody levels were determined. IL-4 and IFN-γ levels in BALF were also examined. Sensitization with the low dose, but not high dose, OVA induced a Th2 dominant condition (elevated IL-4 and decreased IFN-γ levels) in both age. In both age, BHR, BALF eosinophilia, the cellular infiltration, goblet cell metaplasia (GCM), and IgE antibody levels were more prominent in mice sensitized with the low dose than in those with high dose. Among these responses, only GCM was more remarkable in juvenile mice than in adult animals, whereas inverse relation was the case for other parameters. These results indicate that GCM, and consequently, mucus hypersecretion may be an important component of allergic airway inflammation of juvenile animals.
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