Supplemental and Highly Elevated Tocopherol Doses Differentially Regulate Allergic Inflammation: Reversibility of α-Tocopherol and γ-Tocopherol's Effects

We have reported that supplemental doses of the alpha- and gamma-tocopherol isoforms of vitamin E decrease and increase, respectively, allergic lung inflammation. We have now assessed whether these effects of tocopherols are reversible. For these studies, mice were treated with Ag and supplemental tocopherols in a first phase of treatment followed by a 4-wk clearance phase, and then the mice received a second phase of Ag and tocopherol treatments. The proinflammatory effects of supplemental levels of gamma-tocopherol in phase 1 were only partially reversed by supplemental alpha-tocopherol in phase 2, but were completely reversed by raising alpha-tocopherol levels 10-fold in phase 2. When gamma-tocopherol levels were increased 10-fold (highly elevated tocopherol) so that the lung tissue gamma-tocopherol levels were equal to the lung tissue levels of supplemental alpha-tocopherol, gamma-tocopherol reduced leukocyte numbers in the lung lavage fluid. In contrast to the lung lavage fluid, highly elevated levels of gamma-tocopherol increased inflammation in the lung tissue. These regulatory effects of highly elevated tocopherols on tissue inflammation and lung lavage fluid were reversible in a second phase of Ag challenge without tocopherols. In summary, the proinflammatory effects of supplemental gamma-tocopherol on lung inflammation were partially reversed by supplemental levels of alpha-tocopherol but were completely reversed by highly elevated levels of alpha-tocopherol. Also, highly elevated levels of gamma-tocopherol were inhibitory and reversible in lung lavage but, importantly, were proinflammatory in lung tissue sections. These results have implications for future studies with tocopherols and provide a new context in which to review vitamin E studies in the literature. The Journal of Immunology, 2011, 186: 3674-3685.