title: Vitamin E, γ-tocopherol, reduces airway neutrophil recruitment after inhaled endotoxin challenge in rats and in healthy volunteers.
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.
authors: Center for Environmental Medicine, Asthma, & Lung Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA. Michelle_Hernandez@med.unc.edu
authors: Michelle L
authors: ML
authors: Hernandez
authors: James G
authors: JG
authors: Wagner
authors: Aline
authors: A
authors: Kala
authors: Katherine
authors: K
authors: Mills
authors: Heather B
authors: HB
authors: Wells
authors: Neil E
authors: NE
authors: Alexis
authors: John C
authors: JC
authors: Lay
authors: Qing
authors: Q
authors: Jiang
authors: Hongtao
authors: H
authors: Zhang
authors: Haibo
authors: H
authors: Zhou
authors: David B
authors: DB
authors: Peden
mesh_terms: D000328:Adult; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress; D051381:Rats; D013183:Sputum / Q000166:cytology / Q000187:drug effects; D024504:gamma-Tocopherol / Q000008:administration & dosage*
chemical_list: D008070:Lipopolysaccharides; D024504:gamma-Tocopherol
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