ToxSci Advance Access originally published online on March 31, 2004
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Toxicological Sciences 79, 315-325 (2004)
Toxicological Sciences vol. 79 no. 2 © Society of Toxicology; all rights reserved.
Allergic Rhinitis Induced by Intranasal Sensitization and Challenge with Trimellitic Anhydride but Not with Dinitrochlorobenzene or Oxazolone in A/J Mice
* Department of Pharmacology and Toxicology, and Department of Pathobiology and Diagnostic Investigation, Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824
Received October 15, 2003; accepted February 2, 2004
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-
. 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.
Key Words: murine; allergic rhinitis; intranasal instillation; trimellitic anhydride; dinitrochlorobenzene; oxazolone.
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