title: Allergen-stimulated release of thromboxane A2 and leukotriene E4 in humans. Effect of indomethacin.
abstract: Allergen-stimulated release of a cyclooxygenase product (thromboxane [TX] A2) and a 5-lipoxygenase product (leukotriene [LT] E4) into the urine was measured in 10 atopic asthmatics undergoing allergen inhalation. Because indomethacin has been reported to increase allergic-stimulated 5-lipoxygenase product formation and to inhibit the late asthmatic response, we determined the effect of indomethacin (50 mg 3 times a day) or placebo on airway and biochemical responses to inhaled allergen in a randomized, blinded study. Urinary levels of the enzymatic metabolite of TXB2, 11-dehydro-TXB2, increased from 585 +/- 330 to 1,500 +/- 250 pg/mg creatinine (mean +/- SEM, p less than 0.05) 2 h after allergen. Urinary LTE4 increased from 190 +/- 37 to 1,100 +/- 400 (p less than 0.05) 2 h after challenge. The urinary levels of these eicosanoids were not elevated during the late response. Indomethacin significantly reduced urinary 11-dehydro-TXB2 levels without affecting the excretion of LTE4 or pulmonary function. Thus, we failed to obtain evidence for enhanced leukotriene formation during allergic stimulation in vivo in the presence of cyclooxygenase inhibition. Furthermore, we conclude that cyclooxygenase products are likely to play only a marginal role in allergic bronchoconstriction.
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee.
authors.forename: K
authors.initials: K
authors.lastname: Sladek
authors.forename: R
authors.initials: R
authors.lastname: Dworski
authors.forename: G A
authors.initials: GA
authors.lastname: Fitzgerald
authors.forename: K L
authors.initials: KL
authors.lastname: Buitkus
authors.forename: F J
authors.initials: FJ
authors.lastname: Block
authors.forename: S R
authors.initials: SR
authors.lastname: Marney
authors.forename: J R
authors.initials: JR
authors.lastname: Sheller
mesh_terms: D000328:Adult; D000485:Allergens; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology; D001249:Asthma / Q000175:diagnosis / Q000378:metabolism*; D001985:Bronchial Provocation Tests; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D017999:Leukotriene E4; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011897:Random Allocation; D013189:SRS-A / Q000031:analogs & derivatives* / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism*
chemical_list: D000485:Allergens; D013189:SRS-A; D013928:Thromboxane A2; D017999:Leukotriene E4; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin