Effects of Alpha Tocopherol and Probucol Supplements on Allergen-Induced Airway Inflammation and Hyperresponsiveness in a Mouse Model of Allergic Asthma

Abstract

Objective: We investigated the role of antioxidants in airway hyperresponsiveness to acetylcholine using young asthma model mice, which were sensitized and stimulated with ovalbumin. Methods: The mice had been fed either a normal diet, an α-tocopherol-supplemented diet or a probucol-supplemented diet 14 days before the first sensitization. They were immunized with antigen at intervals of 12 days and, starting from 10 days after the second immunization, they were exposed to antigen 3 times every 4th day using an ultrasonic nebulizer. Twenty-four hours after the last antigen inhalation, airway responsiveness to acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was collected. A blood and lung tissue study was also carried out. Results: Twenty-four hours after the last antigen challenge, both IL-4 and IL-5 in the BALF of α-tocopherol-supplemented mice were significantly decreased. The IL-5 level in probucol-supplemented mice was also decreased, but there was no difference in IL-4 levels. The serum IgE level was decreased in probucol-supplemented mice. Differential cell rates of the fluid revealed a significant decrease in eosinophils due to antioxidant supplementation. Airway hyperresponsiveness to acetylcholine was also repressed in antioxidant-supplemented mice. In histological sections of lung tissue, inflammatory cells and mucus secretion were markedly reduced in antioxidant-supplemented mice. We investigated the antioxidant effect on our model mice by examining 8-isoprostane in BALF and lung tissue, and acrolein in BALF; however, our experiment gave us no evidence of the antioxidant properties of either α-tocopherol or probucol contributing to the reduction of airway inflammation. Conclusion: These findings indicate that α-tocopherol and probucol suppress allergic responses in asthma model mice, although these two drugs cause suppression in different ways that are unrelated to antioxidation.

Session 1: Allergic disease Nutrition as a potential determinant of asthma

“…Vitamin E has many effects on the immune system, with reduced vitamin E status promoting the Th2 phenotype either by reducing IFN-g secretion and/or increasing IL-4 or IL-5 secretion by Th-cells (105)(106)(107)(108)(109) . Several mechanisms have been proposed for these immunomodulatory effects.…”

“…Vitamin E may also influence the development of regulatory T-cells (110) . The effects of vitamin E on the immune system appear to be age related, enhancing the IFN-g responses of young but not old mice (111) , and in human subjects naïve Th-cells are more responsive than memory Th-cells to vitamin E (105,(107)(108)(109) . These age-dependent associations may explain the ineffectiveness of vitamin E supplementation in adults with asthma; conversely, any putative effects of vitamin E on asthma may be most potent in early infancy during initial encounters with allergens rather than after disease has been established.…”

Two Faces of Vitamin E in the Lung

“…Thus, we have demonstrated opposing and competing functions of a-tocopherol and g-tocopherol in vivo. Okamoto and colleagues (32) found that feeding mice a-tocopherol starting 2 weeks before antigen sensitization did not affect IgE levels but did reduce the number of eosinophils in the bronchoalveolar lavage. However, the form and purity of a-tocopherol were not indicated.…”

Deficiency of gp91phox Inhibits Allergic Airway Inflammation

“…This has led to much investigation into the relationship between antioxidants and asthma. Dietary antioxidant supplementation attenuated established allergic airway inflammation in some animal models (17)(18)(19)(20)(21)(22). However, clinical trials failed to show a definitive benefit from antioxidant supplementation in humans with asthma (23)(24)(25)(26)(27), and some have even shown harm (28).…”