Vitamin E isoforms and doses differentially regulate experimental asthma

We have reported that supplemental doses of the alpha and gammatocopherol 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 to copherol doses in humans, we examined the regulation of murine experimental asthma by highly-elevated doses of to copherols,defined as 2 mg tocopherol/day (equal to 10 times the supplemental dose). Mice treated with highly-elevated doses of alpha or gammato copherol had significantly higher tissue levels of tocopherols,decreased leukocyte infiltration into the lung, and decreased Th2 cytokine and chemokine production. The reversibility o ftocopherols' 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 iso forms. 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.