Vitamin E isoforms and doses differentially regulate experimental asthma. (97.9)

Abstract

Abstract We have reported that supplemental doses of the alpha and gamma tocopherol isoforms of vitamin E decrease and increase, respectively, lung inflammation in murine experimental asthma. Because asthma clinical trials are currently examining the effect of highly-elevated tocopherol doses in humans, we examined the regulation of murine experimental asthma by highly-elevated doses of tocopherols, defined as 2 mg tocopherol/day (equal to 10 times the supplemental dose). Mice treated with highly-elevated doses of alpha or gamma tocopherol had significantly higher tissue levels of tocopherols, decreased leukocyte infiltration into the lung, and decreased Th2 cytokine and chemokine production. The reversibility of tocopherols’ effects was also determined. At either supplemental or highly-elevated doses, the regulatory effects of alpha and gamma tocopherol were fully reversible, revealing no sustained anti- or pro-inflammatory functions of these isoforms. Overall, gamma tocopherol enhances inflammation at supplemental doses and ablates inflammation at highly-elevated doses. In contrast, alpha tocopherol decreases inflammation at all doses tested. Our results have clinical implications for tocopherol supplementation and alter interpretation of tocopherol studies reported in the literature.