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Inhibition of Airway Inflammation and Hyperreactivity by a Catalytic Antioxidant* FREE TO VIEW

Ling Yi Chang, PhD; James D. Crapo, MD, FCCP
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*From the National Jewish Medical and Research Center, Denver, CO.

Correspondence to: Ling Yi Chang, PhD, 1400 Jackson St, K708, Denver, CO 80206; e-mail: changl@njc.org

Chest. 2003;123(3_suppl):446S. doi:10.1378/chest.123.3_suppl.446S
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A catalytic antioxidant, AEOL 10113 (Incara Pharmaceuticals; Research Triangle Park, NC), was used in a murine model of asthma to test the hypothesis that oxidants contribute to the pathogenesis of asthma. BALB/c mice were immunized and challenged with ovalbumin. AEOL 10113 was administered to mice by intratracheal instillation during ovalbumin challenges. Enhanced pause as an indicator of airway reactivity and differential cell count of lavage cells as an indicator of airway inflammation were assessed. Lung expressions of the adhesion molecules vascular cell adhesion molecule-1 and intracellular cell adhesion molecule-1 were measured. We found that treatment of ovalbumin-challenged mice with AEOL 10113 drastically reduced the severity of airway inflammation as evidenced by an 80% reduction of the total numbers of ovalbumin-induced influx of eosinophils, neutrophils, and lymphocytes in BAL fluid. Inhibition of ovalbumin-induced airway inflammation is associated with inhibited expression of vascular cell adhesion molecule-1, a key adhesion molecule responsible for the recruitment of inflammatory cells into the lungs of ovalbumin-challenged mice. In addition, treatment with AEOL 10113 reduced the magnitude of ovalbumin-induced airway hyperreactivity to methacholine. Enhanced pause measured from AEOL 10113-treated mice was 30% and 25% lower than untreated mice at 30 mg/mL and 40 mg/mL of methacholine, respectively. These results suggest that oxidative stress is an important factor in the pathogenesis of airway inflammation and hyperreactivity, and that the catalytic antioxidant AEOL 10113 can potentially be used for the treatment of asthma.




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