Spectrum of Prostanoid Release after Bronchoalveolar Allergen Challenge in Atopic Asthmatics and in Control Groups: An Alteration in the Ratio of Bronchoconstrictive to Bronchoprotective Mediators

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Abstract
Prostanoids have been implicated in the pathogenesis of asthma because of their potential role in the modulation of airway tone. In the present study, the bronchoconstrictors prostaglandin D2 (PGD2) and thromboxane (TX), and those prostanoids able to protect against bronchoconstriction, prostaglandin E2 (PGE2), and the stable metabolite of prostacyclin, 6-keto-prostaglandin F1α (6-keto-PGF1α), were measured in bronchoalveolar lavage fluid (BALF) before and 5 min after endobronchial allergen challenge in four subject groups: nonatopic nonasthmatics (n = 6), nonatopic asthmatics (n = 3), atopic nonasthmatics (n = 9), and atopic asthmatics (n = 8). There were no significant differences in prechallenge prostanoid levels between the four groups, with the potentially bronchoprotective mediators present in highest concentration. Allergen challenge in atopic asthmatics resulted in significant increases (p < 0.05) in PGD2 (97.4 ± 19.4 to 1,053.2 ± 338.6 pg/ml, mean ± SEM) and TX (45.5 ± 7.5 to 150.7 ± 37.8 pg/ml) over prechallenge levels and control groups. Similarly, histamine increased in the atopic asthmatics after challenge (0.36 ± 0.22 to 6.84 ± 1.86 ng/ml; p < 0.05). Atopic nonasthmatics had slight increases in PGD2 (96.9 ± 25.4 to 219.7 ± 47.5 pg/ml; p > 0.1) after challenge, whereas PGD2 and TX did not change in nonatopic subjects. A significant positive correlation was found between histamine, PGD2, and TX levels after challenge among all groups (p < 0.001). There were no significant changes among the four groups after allergen challenge in 6-keto-PGF1α or PGE2. The ratio of combined bronchoconstrictors (PGD2 + TX) to combined bronchoprotectors(6-keto-PGF1α + PGE2 increased greater than 5-fold in atopic asthmatics after challenge, whereas atopic nonasthmatics increased less than 1-fold and nonatopic subjects did not change (p < 0.001). Thus, atopic asthmatics generated greater amounts of PGD2 and TX than did the three control groups after allergen challenge. The increase in bronchoconstrictors in atopic asthmatics compared with bronchoprotective mediators suggests that the magnitude and relative distribution of the prostanoids produced in response to allergen may be altered in atopic asthma and important in its pathogenesis.