Neutrophil elastase/alpha 1-proteinase inhibitor complex levels decrease in plasma of cystic fibrosis patients during long-term oral beta-carotene supplementation.
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.
Winklhofer-Roob
B M
BM
Department of Pediatrics, University of Zurich, Switzerland.
Schlegel-Haueter
S E
SE
Khoschsorur
G
G
van't Hof
M A
MA
Suter
S
S
Shmerling
D H
DH
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*
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