Am. J. Respir. Crit. Care Med., Volume 160, Number 6, December 1999, 1947-1951

Allergen-induced Synthesis of F₂-Isoprostanes in Atopic Asthmatics
Evidence for Oxidant Stress

RYSZARD DWORSKI, JOHN J. MURRAY, L. JACKSONROBERTS II, JOHN A. OATES, JASON D. MORROW, LAURA FISHER, and JAMES R. SHELLER

Center for Lung Research and Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenessee

It is thought that reactive oxygen species (ROS) participate in the inflammation which characterizes asthma, but the evidence supporting this contention is incomplete. F₂-isoprostanes (F₂-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 F₂-IsoPs in 11 patients with mild atopic asthma after inhaled allergen challenge. The excretion of F₂-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 F₂-IsoPs remained unchanged after inhaled methacholine challenge. In nine atopic asthmatics, F₂-IsoPs were quantified in bronchoalveolar lavage fluid (BALF) at baseline values and in a separate segment 24 h after allergen instillation. F₂-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. Dworski R, Murray JJ, Roberts LJ, II, Oates JA, Morrow JD, Fisher L, Sheller JR. Allergen-induced sythesis of F₂-isoprostanes in atopic asthmatics: evidence for oxident stress.

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