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

Dworski R, Murray JJ, Roberts LJ, Oates JA, Morrow JD, Fisher L, Sheller JR
Am J Respir Crit Care Med. 1999 160 (6): 1947-51

PMID: 10588611 · 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.

MeSH Terms (21)

Administration, Inhalation Adult Allergens Asthma Beclomethasone Bronchial Provocation Tests Bronchoalveolar Lavage Fluid Cross-Over Studies Cyclooxygenase Inhibitors Double-Blind Method Forced Expiratory Volume Glucocorticoids Humans Hypersensitivity, Immediate Mass Spectrometry Methacholine Chloride Middle Aged Oxidative Stress Prostaglandins F Reactive Oxygen Species Skin Tests

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