title: Vitamin E reduces transendothelial migration of neutrophils and prevents lung injury in endotoxin-induced airway inflammation.
abstract: We investigated the pharmacologic effects of the antioxidant Vitamin E (alpha-tocopherol [alpha-toc]) in airway inflammation induced by inhaled endotoxin. A preparation of alpha-toc incorporated in liposomes was administered intraperitoneally in mice 1 h after exposure of aerosolized endotoxin. Injection of 50 mg alpha-toc/kg significantly decreased the number of neutrophils in airspaces and prevented lung injury, monitored both as decreased lactate dehydrogenase activity in airways and reduced lung edema when compared with animals treated with plain liposomes. Immunofluorescence staining of lung tissue revealed that treatment with alpha-toc decreased the number of neutrophils in lung interstitium, whereas the number in lung blood vessels and peripheral blood did not differ between mice treated with alpha-toc and control mice. Our results indicate that alpha-toc downmodulates the migration of neutrophils across the endothelial barrier, but in contrast to strong anti-inflammatory drugs such as corticosteroids, without inhibition of transcription factors involved in the early inflammatory response (nuclear factor-kappaB/activator protein-1). Neither was the endotoxin-induced expression of proinflammatory cytokines in lung tissue downregulated. Treatment with a combination of alpha-toc and a suboptimal dose of 0.5 mg/kg dexamethasone enhanced the effect, suggesting that alpha-toc, in combination with low doses of corticosteroids, might be effective for therapeutic treatment of acute lung injury.
authors.affiliation: Department of Medical Countermeasures, Divison of NBC Defence, Swedish Defence Research Agency, Umeå, Sweden. david.rocksen@foi.se
authors.forename: David
authors.initials: D
authors.lastname: Rocksén
authors.forename: Barbro
authors.initials: B
authors.lastname: Ekstrand-Hammarström
authors.forename: Lenore
authors.initials: L
authors.lastname: Johansson
authors.forename: Anders
authors.initials: A
authors.lastname: Bucht
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D003907:Dexamethasone / Q000008:administration & dosage; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D055370:Lung Injury; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014810:Vitamin E; D003907:Dexamethasone