Vitamin E, γ-tocopherol,reduces airway neutrophil recruitment after inhaled endotoxin challenge in rats and in healthy volunteers |
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| Institution: | 1. Center for Environmental Medicine, Asthma, & Lung Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA;2. Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA;3. Department of Nutrition Science, College of Health and Human Sciences, Purdue University, West Lafayette, IN 47907, USA;4. Department of Biostatistics, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA;1. Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria;2. Department of Chemistry, Ahmadu Bello University, Zaria, Nigeria;3. Department of Pharmaceutical and Medicinal Chemistry, Ahmadu Bello University, Zaria, Nigeria;4. Department of Biochemistry, Kano University of Science and Technology, Wudil, Kano, Nigeria;1. Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China;2. Department of Laboratory, Jining No 1 People''s Hospital, Jining, Shangdong, China;1. Comparative Internal Medicine Laboratory, Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, United States;2. Auburn University, College of Veterinary Medicine, Auburn, AL, United States;1. Division of Metabolic and Bariatric Surgery, Hartford Hospital, Hartford, Connecticut;2. Genetic Research Center, Hartford Hospital, Hartford, Connecticut;1. Translational Research Unit, Comenius University, Faculty of Medicine, Bratislava, Slovakia;2. Department of Clinical Trials, National Cancer Institute, Bratislava, Slovakia;3. 1st Department of Oncology, Comenius University, Faculty of Medicine and St. Elisabeth Cancer Institute, Bratislava, Slovakia;4. Cancer Research Institute, Biomedical Center, Slovak Academy of Sciences, Bratislava, Slovakia;5. Oncohematology Clinic, National Cancer Institute, Bratislava, Slovakia;6. 2nd Department of Oncology, Comenius University, Faculty of Medicine and National Cancer Institute, Bratislava, Slovakia;7. Clinic of Clinical Oncology, National Cancer Institute, Bratislava, Slovakia;8. Department of Medical Oncology of St. Elizabeth University of Health and Social Sciences and St. Elisabeth Cancer Institute, Bratislava, Slovakia;9. Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University, Faculty of Medicine, Bratislava, Slovakia |
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| 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 (20 μg) 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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