alpha-Lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma.

摘要

BACKGROUND: Oxidative stress may play an important role in the pathogenesis of bronchial asthma. OBJECTIVE: We evaluated the therapeutic effect of alpha-lipoic acid, a nonenzymatic antioxidant, in a mouse model of asthma. METHODS: BALB/c mice were immunized intraperitoneally with ovalbumin (OVA) on days 1 and 14 and challenged with inhaled OVA on days 28, 29, and 30. Mice were fed OVA-free standard mouse chow with 0%, 0.125%, 0.25%, 0.5%, and 1% (wt/wt) alpha-lipoic acid during the immunization and challenge periods. On day 31, mice were challenged with inhaled methacholine, and enhanced pause was measured as an index of airway hyperresponsiveness. Severity of airway inflammation was determined by means of differential cell count of bronchoalveolar lavage (BAL) fluid and by means of histopathologic lung analysis. Levels of OVA-specific IgE in serum, IL-4 and IL-5 in BAL fluid, and intracellular reactive oxygen species in alveolar macrophages and lymphocytes obtained from regional perihilar lymph nodes were measured. Nuclear factor kappaB DNA-binding activity in lung tissues was analyzed by means of electrophoretic gel mobility shift assay. RESULTS: Compared with untreated asthmatic mice, mice treated with alpha-lipoic acid had significantly reduced airway hyperresponsiveness, a lower proportion of eosinophils among BAL cells, and significantly improved pathologic lesion scores of the lungs. alpha-Lipoic acid also significantly reduced serum OVA-specific IgE concentrations, IL-4 and IL-5 concentrations in BAL fluid, and intracellular reactive oxygen species and nuclear factor kappaB DNA-binding activity. CONCLUSION: These results suggest that oxidative stress plays an important role in asthmatic airway inflammation and that alpha-lipoic acid may be useful as adjuvant therapy for bronchial asthma.