title: Supplemental and highly elevated tocopherol doses differentially regulate allergic inflammation: reversibility of α-tocopherol and γ-tocopherol's effects.
abstract: We have reported that supplemental doses of the α- and γ-tocopherol isoforms of vitamin E decrease and increase, respectively, allergic lung inflammation. We have now assessed whether these effects of tocopherols are reversible. For these studies, mice were treated with Ag and supplemental tocopherols in a first phase of treatment followed by a 4-wk clearance phase, and then the mice received a second phase of Ag and tocopherol treatments. The proinflammatory effects of supplemental levels of γ-tocopherol in phase 1 were only partially reversed by supplemental α-tocopherol in phase 2, but were completely reversed by raising α-tocopherol levels 10-fold in phase 2. When γ-tocopherol levels were increased 10-fold (highly elevated tocopherol) so that the lung tissue γ-tocopherol levels were equal to the lung tissue levels of supplemental α-tocopherol, γ-tocopherol reduced leukocyte numbers in the lung lavage fluid. In contrast to the lung lavage fluid, highly elevated levels of γ-tocopherol increased inflammation in the lung tissue. These regulatory effects of highly elevated tocopherols on tissue inflammation and lung lavage fluid were reversible in a second phase of Ag challenge without tocopherols. In summary, the proinflammatory effects of supplemental γ-tocopherol on lung inflammation were partially reversed by supplemental levels of α-tocopherol but were completely reversed by highly elevated levels of α-tocopherol. Also, highly elevated levels of γ-tocopherol were inhibitory and reversible in lung lavage but, importantly, were proinflammatory in lung tissue sections. These results have implications for future studies with tocopherols and provide a new context in which to review vitamin E studies in the literature.
authors.affiliation: Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: McCary
authors.forename: Hiam
authors.initials: H
authors.lastname: Abdala-Valencia
authors.forename: Sergejs
authors.initials: S
authors.lastname: Berdnikovs
authors.forename: Joan M
authors.initials: JM
authors.lastname: Cook-Mills
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D019587:Dietary Supplements; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012130:Respiratory Hypersensitivity / Q000473:pathology* / Q000517:prevention & control*; D015854:Up-Regulation / Q000187:drug effects; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000097:blood; D024504:gamma-Tocopherol / Q000008:administration & dosage* / Q000097:blood
chemical_list: D018836:Inflammation Mediators; D024504:gamma-Tocopherol; D024502:alpha-Tocopherol