Trimellitic anhydride (TMA) is a reactive, low-molecular-weight (LMW) chemical known to induce IgE and occupational asthma. We have previously shown that dermal powder sensitization with subsequent TMA airway challenge produces both early (EAR) and late-phase airway responses (LAR) in Brown Norway rats (BNR). The response to TMA challenge is characterized by pulmonary eosinophilia, hemorrhage and early, short and late, prolonged (hrs) increases in Penh (an index of airway resistance). The pathological and physiological responses in this model are consistent with that seen in TMA asthmatics. Clinically, bronchodilators have been noted to be effective in reversing EAR, but not LAR; corticosteroids, given prophylactically, inhibit LAR, presumably due to their anti-inflammatory activity. The effect of the corticosteroid, dexamethasone, and the B2, agonist, salbutamol, on the TMA-LAR was examined in the present study to further assess the utility of the BNR-TMA asthma model. BNR were sensitized by 4 weekly, 4 hr dermal applications of 40 mg TMA powder. Two weeks after the final dermal application they received a 10 min, 40 mg/m3 TMA inhalation challenge with or without prior treatment of dexamethasone (2mg/kg i.p. for 3 days). Following TMA challenge, Penh was recorded for 16-20 hrs. In a separate group, BNR were exposed to a 1% salbutamol aerosol for 10 min either 30 min before TMA challenge or during the LAR. All TMA sensitized, non-treated BNR (8/8) developed LAR following challenge. LAR Penh increase and airway (bronchoalveolar lavage) eosinophilia were completely inhibited in all animals when treated with dexametisone. Salbutamol had no effect on LAR when given either prior to challenge, or during the LAR. It is concluded that the effects of corticosteroid and B2 agonist in the LAR BNR-TMA model are similar to that observed in human TMA asthma suggesting the potential utility of this model in the study of LAR to LMW asthmagens.
Proceedings of the American Thoracic Society. 2005 ATS International Conference, May 20-25, 2005, San Diego, California