Urinary excretion of leukotriene E4 and 11-dehydro-thromboxane B2 in response to bronchial provocations with allergen, aspirin, leukotriene D4, and histamine in asthmatics.
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 creatinine). 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 creatinine; 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 less than 0.001). The findings support that the cysteinyl-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Kumlin
M
M
Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
Dahlén
B
B
Björck
T
T
Zetterström
O
O
Granström
E
E
Dahlén
S E
SE
D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage; D001249:Asthma / Q000503:physiopathology / Q000652:urine*; D001985:Bronchial Provocation Tests; D005260:Female; D006632:Histamine; D006801:Humans; D017999:Leukotriene E4; D008297:Male; D008875:Middle Aged; D013189:SRS-A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000652:urine; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine
D000485:Allergens; D013189:SRS-A; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D017999:Leukotriene E4; D006632:Histamine; D001241:Aspirin