Vitamin E, γ-tocopherol, reduces airway neutrophil recruitment after inhaled endotoxin challenge in rats and in healthy volunteers
Michelle L Hernandez, James G Wagner, Aline Kala, Katherine Mills, Heather B Wells, Neil E Alexis, John C Lay, Qing Jiang, Hongtao Zhang, Haibo Zhou, David B Peden, Michelle L Hernandez, James G Wagner, Aline Kala, Katherine Mills, Heather B Wells, Neil E Alexis, John C Lay, Qing Jiang, Hongtao Zhang, Haibo Zhou, David B Peden
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.
Conflict of interest statement
Disclosures: D. B. Peden has been a consultant to GlaxoSmithKline and Aquinox Pharmaceuticals and a contract with MedImmune. The rest of the authors have declared that they have no conflicts of interest.
Copyright © 2013 Elsevier Inc. All rights reserved.
Figures
Source: PubMed