Center for Environmental Medicine, Asthma, & Lung Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA.
Free Radic Biol Med. 2013 Jul;60:56-62. doi: 10.1016/j.freeradbiomed.2013.02.001. Epub 2013 Feb 9.
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.
流行病学研究表明，膳食维生素 E 是哮喘的重要候选干预措施。我们的研究小组已经表明，在啮齿动物和人体 I 期研究中，每日摄入维生素 E（γ-生育酚，γT）具有抗炎作用。本研究的目的是测试 γT 补充剂是否可以减轻大鼠和健康人类志愿者中性粒细胞性气道炎症模型。F344/N 大鼠随机接受 γT 口服灌胃或安慰剂，然后用鼻内 LPS（20μg）进行挑战。支气管肺泡灌洗液和肺组织学用于评估气道中性粒细胞募集。在 IIa 期临床研究中，13 名非哮喘受试者完成了一项双盲、安慰剂对照交叉研究，他们分别服用富含 γT 的胶囊或葵花籽油安慰剂胶囊。每日补充 7 天后，他们接受了吸入 LPS 挑战。吸入 LPS 后 6 小时评估诱导痰中的中性粒细胞。使用重复测量方差分析比较 LPS 后 γT 与安慰剂对气道中性粒细胞的影响。在大鼠中，口服 γT 补充剂可显著减少经鼻内 LPS 挑战引起的组织浸润（p<0.05）和气道中性粒细胞积聚（p<0.05）。在人类志愿者中，与安慰剂相比，γT 治疗可显著降低诱导痰中的中性粒细胞（p=0.03）。口服 γT 补充剂可减少大鼠和人类吸入 LPS 挑战模型中的气道中性粒细胞募集。这些结果表明，γT 可能是治疗疾病人群中性粒细胞性气道炎症的潜在治疗候选药物。
