Allergen-induced synthesis of F(2)-isoprostanes in atopic asthmatics. Evidence for oxidant stress

Am J Respir Crit Care Med. 1999 Dec;160(6):1947-51. doi: 10.1164/ajrccm.160.6.9903064.


It is thought that reactive oxygen species (ROS) participate in the inflammation which characterizes asthma, but the evidence supporting this contention is incomplete. F(2)-isoprostanes (F(2)-IsoPs) are arachidonate products formed on membrane phospholipids by the action of ROS and thereby represent a quantitative measure of oxidant stress in vivo. Using a mass spectrometric assay we measured urinary release of F(2)-IsoPs in 11 patients with mild atopic asthma after inhaled allergen challenge. The excretion of F(2)-IsoPs increased at 2 h after allergen (1.5 +/- 0.2 versus 2.6 +/- 0.3 ng/mg creatinine) and remained significantly elevated in all urine collections for the 8-h period of the study (analysis of variance [ANOVA]). The measured compounds were of noncyclooxygenase origin because neither aspirin nor indomethacin given before challenge suppressed them. Urinary F(2)-IsoPs remained unchanged after inhaled methacholine challenge. In nine atopic asthmatics, F(2)-IsoPs were quantified in bronchoalveolar lavage fluid (BALF) at baseline values and in a separate segment 24 h after allergen instillation. F(2)-IsoPs were elevated late in the BALF (0.9 +/- 0.2 versus 11.4 +/- 3.0 pg /ml, baseline versus allergen, respectively, p = 0.007). The increase was inhibited by pretreatment of the subjects with inhaled corticosteroids. These findings provide a new evidence for a role for ROS and lipid peroxidation in allergen-induced airway inflammation.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Adult
  • Allergens*
  • Asthma / drug therapy
  • Asthma / immunology
  • Asthma / metabolism*
  • Asthma / physiopathology
  • Beclomethasone / administration & dosage
  • Bronchial Provocation Tests*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cross-Over Studies
  • Cyclooxygenase Inhibitors / pharmacology
  • Double-Blind Method
  • Forced Expiratory Volume
  • Glucocorticoids / administration & dosage
  • Humans
  • Hypersensitivity, Immediate / complications
  • Hypersensitivity, Immediate / metabolism
  • Mass Spectrometry
  • Methacholine Chloride
  • Middle Aged
  • Oxidative Stress*
  • Prostaglandins F / biosynthesis*
  • Prostaglandins F / urine
  • Reactive Oxygen Species / physiology
  • Skin Tests


  • Allergens
  • Cyclooxygenase Inhibitors
  • Glucocorticoids
  • Prostaglandins F
  • Reactive Oxygen Species
  • Methacholine Chloride
  • Beclomethasone