Urinary Excretion of Leukotriene E4 and 11-dehydro-Thromboxane B2 in Response to Bronchial Provocations with Allergen, Aspirin, Leukotriene D4, and Histamine …

M Kumlin, B Dahlén, T Björck, O Zetterström… - American Review of …, 1992 - atsjournals.org
M Kumlin, B Dahlén, T Björck, O Zetterström, E Granström, SE Dahlén
American Review of Respiratory Disease, 1992atsjournals.org
In vivo production of thromboxane (TX) A2 and the cysteinyl-containing leukotrienes (LT) C4,
D4, and E4 in correlation to airway responses was studied. Bronchial provocation with
specific allergen in atopic asthmatics was followed by a significant increase in urinary
concentration of immunoreactive LTE4 (34±6 before versus 56±7 ng/mmol creatinine after
allergen challenge; n= 5) and 11-dehydro-TXB2 (164±29 versus 238±25 ng/mmol
creatlnine). In the presence of the leukotriene-antagonist ICI-204,219, which significantly …
In vivo production of thromboxane (TX) A2 and the cysteinyl-containing leukotrienes (LT) C4, D4, and E4 in correlation to airway responses was studied. Bronchial provocation with specific allergen in atopic asthmatics was followed by a significant increase in urinary concentration of immunoreactive LTE4 (34 ± 6 before versus 56 ± 7 ng/mmol creatinine after allergen challenge; n = 5) and 11-dehydro-TXB2 (164 ± 29 versus 238 ± 25 ng/mmol creatlnine). In the presence of the leukotriene-antagonist ICI-204,219, which significantly increased the PD20 for allergen, the increment in urinary excretion of LTE4 was even higher (60 ± 8 versus 288 ± 128 ng/mmol creatlnine; n = 5). In contrast, provocation with histamine (n = 5) did not provoke release of leukotrienes or thromboxane, nor was inhalation of LTD4 (n = 7) associated with increased urinary concentration of 11-dehydro-TXB2. Furthermore, bronchoconstriction induced by inhalation of lysine-aspirin in aspirin-sensitive asthmatics (n = 4) was followed by increased levels of LTE4 in the urine, whereas the levels of 11-dehydro-TXB2 remained the same. Finally, the basal levels of LTE4 in the urine of nine aspirin-sensitive asthmatics were elevated as compared with 15 other asthmatics (112 ± 54 versus 38 ± 20 ng/mmol creatinine; p < 0.001). The findings support that the cystelnyl-leukotrienes are potential mediators of allergen-induced asthma and that the release of LTE4 and 11-dehydro-TXB2 into the urine appeared to be a direct and dose-dependent effect of the antigen-antibody reaction. Moreover, the findings in aspirin-sensitive asthmatics indicate that cysteinyl-leukotrienes may be of particular importance in the pathogenesis of aspirin-asthma.
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