Natural-source d-α-tocopheryl acetate inhibits oxidant stress and modulates atopic asthma in humans in vivo

Background: Asthma is associated with oxidant stress and diminished antioxidant defenses. Yet, the mechanistic role of oxidant stress and antioxidant supplementation in human asthmatics remains uncertain. We determined the effect of high doses of the antioxidant natural-source d-alpha-tocopheryl acetate for 16 weeks on allergen-induced airway oxidant stress, inflammation, and bronchial responsiveness to methacholine and allergen in atopic asthmatics in vivo. Methods: Thirty-three mild atopic asthmatics underwent bronchoscopy with baseline bronchoalveolar lavage and segmental allergen challenge. The allergen-challenged airway was lavaged 24 h later. At least 3 weeks later, patients underwent inhaled challenges with methacholine and specific allergen. Volunteers took 1500 IU of natural-source d-alpha-tocopheryl acetate daily for at least 16 weeks. At the end of the treatment, the two bronchoscopies and inhaled methacholine and allergen challenges were repeated. F-2-isoprostanes, specific markers of oxidant stress, and selected Th1 and Th2 cytokines were analyzed in the lavage fluid. Results: Following supplementation of natural-source d-alpha-tocopheryl acetate, plasma concentrations of a-tocopherol increased and gamma-tocopherol decreased. Both baseline and allergen-induced F-2-isoprostanes significantly decreased, providing biochemical evidence for an antioxidant effect. Natural-source d-alpha-tocopheryl acetate reduced allergen-provoked concentrations of interleukin 3 and interleukin 4 and augmented levels of interleukin 12 in bronchoalveolar lavage fluid. Natural-source d-alpha-tocopheryl acetate improved airway responsiveness to methacholine but did not alter airway reactivity to specific allergen. Conclusions: Inhibition of oxidant stress by natural-source d-alpha-tocopheryl acetate modulates allergic inflammation and airway hyperresponsiveness in human atopic asthmatics in vivo. These results need to be confirmed by a randomized placebo-controlled trial.