Aerosol-administered alpha-tocopherol attenuates lung inflammation in rats given lipopolysaccharide intratracheally.
Intrapulmonary administration of bacterial lipopolysaccharide (LPS) induces a well-characterized lung inflammatory response involving alveolar macrophage activation, proinflammatory cytokine elaboration, and neutrophil influx. Vitamin E, a lipophilic antioxidant consisting of a family that includes tocopherols and tocotrienols, has previously been shown to have a variety of anti-inflammatory effects, raising interest in its possible uses in disease prevention or therapy. Because aerosol delivery is a specific and rapid way to administer agents to the lungs, the authors undertook to determine whether inhaled vitamin E aerosols would have an anti-inflammatory effect in the lungs. Using a rat model of acute lung inflammation caused by intratracheally administered LPS (10 microg Pseudomonas aeruginosa LPS), the authors examined the effect of aerosol-administered vitamin E, in this case alpha-tocopherol, on several indices of lung inflammation which are increased by LPS treatment. It was found that inhaled alpha-tocopherol aerosol, but not inhaled alpha-tocopherol acetate aerosol, decreased tumor necrosis factor alpha (TNFalpha) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA levels in lung tissue, TNFalpha and CINC-1 immunoreactive protein levels in lung lavage, and the number of neutrophils recoverable by lung lavage from rats given LPS intratracheally. These results contribute to the increasing body of work describing immunomodulatory functions of alpha-tocopherol, and support the idea that direct aerosol administration of alpha-tocopherol may play a beneficial role in strategies to control inflammatory lung illnesses.
Hybertson
Brooks M
BM
Webb-Waring Institute for Cancer, Aging and Antioxidant Research, 4200 East Ninth Avenue, Box C-322, Denver, CO 80262, USA. Brooks.Hybertson@UCHSC.edu
Chung
Jin H
JH
Fini
Mehdi A
MA
Lee
Young M
YM
Allard
Jenny D
JD
Hansen
Brian N
BN
Cho
Okyong J
OJ
Shibao
Gayle N
GN
Repine
John E
JE
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D024502:alpha-Tocopherol / Q000008:administration & dosage*
D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D024502:alpha-Tocopherol