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Forms of Vitamin E have Opposing Effects on Experimental Asthma

We previously reported that the endothelial cell adhesion molecule VCAM‐1 signals through reactive oxygen species generated by NOX2 and that this regulates leukocyte trafficking in vitro and in vivo. Therefore, we determined whether leukocyte migration is modulated by two major dietary forms of the antioxidant vitamin E, (d)‐α‐tocopherol (aT) and (d)‐γ‐tocopherol (gT). Mice were treated daily with physiological levels of aT or gT after sensitization and before challenge with the antigen ovalbumin, a model of experimental asthma. aT significantly inhibited inflammation in the lung and inhibited airway hyperresponsiveness (AHR). Surprisingly, gT exacerbated inflammation and AHR in the lung. Most interestingly, when gT and aT were co‐administered, gT ablated the benefit of aT. In addition, gT antagonized aT inhibition of leukocyte transendothelial migration in vitro. In summary, aT and gT have opposing effects on inflammation. These data have implications on the design and interpretation of clinical studies with mixed tocopherols in supplements and diets. Reported studies indicate that aT is beneficial for experimental asthma in mice and for asthma in Europeans who consume diets low gT but not for Americans who consume diets high in gT, suggesting that differences in the outcomes in these reports on vitamin E may, in part, reflect the opposing effects of α‐tocopoherol and γ‐tocopherol.