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Free Radic Biol Med ; 60: 56-62, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23402870

ABSTRACT

Epidemiologic studies suggest that dietary vitamin E is an important candidate intervention for asthma. Our group has shown that daily consumption of vitamin E (γ-tocopherol, γT) has anti-inflammatory actions in both rodent and human phase I studies. The objective of this study was to test whether γT 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 γT versus placebo, followed by intranasal LPS (20µg) challenge. Bronchoalveolar lavage fluid and lung histology were used to assess airway neutrophil recruitment. In a phase IIa clinical study, 13 nonasthmatic subjects completed a double-blinded, placebo-controlled crossover study in which they consumed either a γT-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 γT compared to placebo on airway neutrophils post-LPS was compared using a repeated-measures analysis of variance. In rats, oral γT 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, γT treatment significantly decreased induced sputum neutrophils (p=0.03) compared to placebo. Oral supplementation with γT reduced airway neutrophil recruitment in both rat and human models of inhaled LPS challenge. These results suggest that γT is a potential therapeutic candidate for prevention or treatment of neutrophilic airway inflammation in diseased populations.


Subject(s)
Asthma/drug therapy , Inflammation/drug therapy , Lung/drug effects , gamma-Tocopherol/administration & dosage , Adult , Animals , Asthma/pathology , Bronchoalveolar Lavage Fluid/chemistry , Female , Humans , Inflammation/pathology , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/toxicity , Lung/pathology , Male , Neutrophil Infiltration/drug effects , Oxidative Stress , Rats , Sputum/cytology , Sputum/drug effects
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