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

Abstract

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.