title: Neutrophil elastase/alpha 1-proteinase inhibitor complex levels decrease in plasma of cystic fibrosis patients during long-term oral beta-carotene supplementation.
abstract: Lung inflammation in cystic fibrosis (CF) is associated with an increased release from activated neutrophils of oxidants and proteinases. Free radical generation is not efficiently neutralized, and the major anti-proteinase, alpha 1-proteinase inhibitor (alpha 1-PI) is thought to be oxidatively inactivated. We hypothesized that enhanced antioxidant protection could represent an additional long-term strategy to attentuate the host inflammatory response. The effect on plasma neutrophil elastase/alpha 1-PI (NE/alpha 1-PI) complex levels (as a marker of lung inflammation) and plasma malondialdehyde concentrations (as a marker of lipid peroxidation) of additional oral beta-carotene supplementation was studied in 33 CF patients who had already received long-term vitamin E supplementation. In the presence of a more than 10-fold increase in plasma beta-carotene concentrations (mean +/- SEM) (0.09 +/- 0.01 to 1.07 +/- 0.19 mumol/L; p < 0.0001), a small increase in plasma alpha-tocopherol concentrations (23.8 +/- 1.31 to 28.4 +/- 1.81 mumol/L; p = 0.02), and a more than 50% decrease in plasma malondialdehyde concentrations (1.00 +/- 0.07 to 0.46 +/- 0.03 mumol/L; p < 0.0001), plasma NE/alpha 1-PI complex levels decreased from 102.2 +/- 16.0 to 83.0 +/- 10.4 micrograms/L; (p = 0.02). Plasma retinol concentrations increased (1.05 +/- 0.06 to 1.23 +/- 0.07 mumol/L; p = 0.0001) due to conversion of beta-carotene to retinol, which could have contributed to the decrease in NE/alpha 1-PI complex levels. Based on these results, we speculate that efficient antioxidant supplementation could attenuate lung inflammation in CF.
authors.affiliation: Department of Pediatrics, University of Zurich, Switzerland.
authors.forename: B M
authors.initials: BM
authors.lastname: Winklhofer-Roob
authors.forename: S E
authors.initials: SE
authors.lastname: Schlegel-Haueter
authors.forename: G
authors.initials: G
authors.lastname: Khoschsorur
authors.forename: M A
authors.initials: MA
authors.lastname: van't Hof
authors.forename: S
authors.initials: S
authors.lastname: Suter
authors.forename: D H
authors.initials: DH
authors.lastname: Shmerling
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000097:blood*; D015842:Serine Proteinase Inhibitors / Q000097:blood*; D014810:Vitamin E / Q000097:blood; D000515:alpha 1-Antitrypsin / Q000378:metabolism*; D019207:beta Carotene / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D008054:Lipid Peroxides; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; C037741:alpha 1-antitrypsin-leukocyte elastase complex; D019207:beta Carotene; D014810:Vitamin E; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase