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Randomized Controlled Trial
. 2013 Jul:60:56-62.
doi: 10.1016/j.freeradbiomed.2013.02.001. Epub 2013 Feb 9.

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

Michelle L Hernandez  1 , 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
Affiliations
Randomized Controlled Trial

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

Michelle L Hernandez et al. Free Radic Biol Med. 2013 Jul.

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.

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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.

Figures

Figure 1
Figure 1. Pre-clinical studies using rats
A) Time Course of treatment with γT (black triangles) and intranasal LPS (up-arrows). Treatment related effects of LPS and γT on B) BALF and C) tissue PMNs collected 24h after the last LPS challenge.
Figure 2
Figure 2. Lung histology in rats
Photomicrographs of lung tissues stained with hematoxylin &eosin from rats after airway treatment with A) saline, B) endotoxin or C) endotoxin and γT. ap=alveolar parenchyma; bv = blood vessel; sa = small airway; arrows indicate inflammatory cell infiltrates. Magnification bar = 20mm.
Figure 3
Figure 3. Phase IIa study design in healthy human volunteers
Randomized, placebo controlled crossover study of a γT-enriched supplement or sunflower oil placebo in 13 healthy volunteers. Subjects were challenged with 20,000 endotoxin units of Clinical Center Reference Endotoxin (CCRE), followed by sputum induction 6 hours after the challenge.
Figure 4
Figure 4. Serum levels of Tocopherols and γ-CEHC during the placebo and active study periods
A). serum γT concentrations B). serum γ-CEHC concentrations C). serum 5-nitro- γT concentrations.
Figure 5
Figure 5. Blood and induced sputum leukocytes
Blood A). Total white blood cell (WBC) count B). Absolute neutrophil count (ANC). Induced sputum C). %neutrophils (%PMNS) and D). %eosinophils. Values were calculated by subtracting the baseline (pre-LPS) %PMN or %eosinophil value to the post-LPS value to assess the deltas. Repeated measures ANOVA was used to calculate the treatment effect.
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References

    1. Gern JE, Busse WW. Relationship of viral infections to wheezing illnesses and asthma. Nat Rev Immunol. 2002;2(2):132–138. - PMC - PubMed
    1. Peden DB. The epidemiology and genetics of asthma risk associated with air pollution. J Allergy Clin Immunol. 2005;115(2):213–219. quiz 220. - PubMed
    1. Reed CE, Milton DK. Endotoxin-stimulated innate immunity: A contributing factor for asthma. J Allergy Clin Immunol. 2001;108(2):157–166. - PubMed
    1. Alexis NE, et al. Development of an inhaled endotoxin challenge protocol for characterizing evoked cell surface phenotype and genomic responses of airway cells in allergic individuals. Ann Allergy Asthma Immunol. 2008;100(3):206–215. - PubMed
    1. Alexis NE, et al. Acute LPS inhalation in healthy volunteers induces dendritic cell maturation in vivo. J Allergy Clin Immunol. 2005;115(2):345–350. - PubMed

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