Allergic airway diseases induced by low molecular weight (LMW) chemicals, including
trimellitic anhydride (TMA), are characterized by airway mucus hypersecretion and an infiltration of eosinophils and lymphocytes. Many experimental models have linked LMW chemical-induced allergic airway disease to Th2
cytokines. Most murine models, however, use dermal exposure to sensitize mice. The present study was designed to test the hypothesis that intranasal sensitization and challenge with the known chemical respiratory
allergen TMA, but not the nonrespiratory sensitizers
dinitrochlorobenzene (
DNCB) and
oxazolone (OXA), will induce characteristic features of LMW chemical-induced allergic airway disease in the nasal and pulmonary airways. A/J mice were intranasally sensitized and challenged with TMA,
DNCB, or OXA. Only mice that were intranasally sensitized and challenged with TMA had a marked
allergic rhinitis with an influx of eosinophils, lymphocytes, and plasma cells, increased intraepithelial mucusubstances, and a regenerative
hyperplasia.
Cytokine mRNA levels in the nasal airway of TMA treated mice also revealed an increase in the
mRNA levels of the Th2
cytokines IL-4,
IL-5, and
IL-13, but no change in the level of the Th1
cytokine IFN-gamma. No lesions were found in the nasal airways of mice exposed to
DNCB or OXA. TMA increased lung-derived
IL-5 mRNA while
DNCB and OXA caused no change in lung-derived
cytokine mRNA levels. Both TMA and
DNCB caused increases in total serum
IgE, unlike OXA-exposed mice. However, no adverse alterations were found microscopically in the lungs of mice treated with TMA,
DNCB, or OXA. This study is the first to demonstrate that
intranasal administration of a known chemical respiratory
allergen is an effective method of sensitization resulting in the hallmark features of
allergic rhinitis after challenge with a concomitant increase in nasal airway-derived Th2
cytokine mRNA, lung-derived
IL-5 mRNA, and total serum
IgE. In contrast,
DNCB and OXA failed to elicit the pathologic changes in the nasal airways and
cytokine changes in the lung. This model may be useful for identifying other chemical respiratory
allergens.