Vitamin E, γ-tocopherol, reduces airway neutrophil recruitment after inhaled endotoxin challenge in rats and in healthy volunteers

Epidemiologic studies suggest that dietary vitamin E is an important candidate intervention for asthma. Our group has shown that daily consumption of vitamin E (gamma-tocopherol, gamma T) has anti-inflammatory actions in both rodent and human phase I studies. The objective of this study was to test whether gamma T supplementation could mitigate a model of neutrophilic airway inflammation in rats and in healthy human volunteers. F344/N rats were randomized to oral gavage with gamma T versus placebo, followed by intranasal LPS (20 mu g) challenge. Bronchoalveolar lavage fluid and lung histology were used to assess airway neutrophil recruitment. In a phase ha clinical study, 13 nonasthmatic subjects completed a double-blinded, placebo-controlled crossover study in which they consumed either a gamma T-enriched capsule or a sunflower oil placebo capsule. After 7 days of daily supplementation, they underwent an inhaled LPS challenge. Induced sputum was assessed for neutrophils 6 h after inhaled LPS. The effect of gamma T compared to placebo on airway neutrophils post-LPS was compared using a repeated-measures analysis of variance. In rats, oral gamma T supplementation significantly reduced tissue infiltration (p < 0.05) and accumulation of airway neutrophils (p <0.05) that are elicited by intranasal LPS challenge compared to control rats. In human volunteers, gamma T treatment significantly decreased induced sputum neutrophils (p=0.03) compared to placebo. Oral supplementation with gamma T reduced airway neutrophil recruitment in both rat and human models of inhaled LPS challenge. These results suggest that gamma T is a potential therapeutic candidate for prevention or treatment of neutrophilic airway inflammation in diseased populations. (C) 2013 Elsevier Inc. All rights reserved.