The role of thromboxane in allergen-induced asthmatic responses.
In this study we evaluated the role of thromboxane in causing allergen-induced early and late asthmatic responses and airway hyperresponsiveness in asthmatic subjects. Twelve atopic subjects with stable asthma and documented early and late asthmatic responses to an inhaled allergen were treated with placebo or CGS 13080, a specific thromboxane synthetase inhibitor, given orally (200 mg four times daily) for two days before, the day of, and the day after allergen inhalation. Treatments were administered in a double-blind, placebo-controlled, crossover fashion. The effect of pretreatment with CGS 13080 was examined on serum TxB2 levels and the magnitude of the asthmatic responses after inhaled allergen. Serum TxB2 levels increased significantly from 96 ng.ml-1 (SEM 29) 3 h after diluent to 151 ng.ml-1 (SEM 27) 3 h after allergen (p = 0.008). CGS 13080 pretreatment markedly inhibited the levels of TxB2 at all time points before and after inhaled allergen (p = 0.0001) and had a small but significant effect on the magnitude of the early asthmatic responses after allergen (p = 0.0009). CGS 13080 did not alter either late asthmatic responses, baseline airway responsiveness, or the increase in histamine airway responsiveness after allergen. These results suggest that allergen-induced early asthmatic responses, but not late responses or allergen-induced airway hyperresponsiveness, are partly caused by thromboxane release.
Manning
P J
PJ
Dept of Medicine, McMaster, University, Hamilton, Ontario, Canada.
Stevens
W H
WH
Cockcroft
D W
DW
O'Byrne
P M
PM
D000328:Adult; D000485:Allergens; D001249:Asthma / Q000209:etiology* / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D011725:Pyridines / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013931:Thromboxanes / Q000502:physiology*; D013997:Time Factors
D000485:Allergens; D007093:Imidazoles; D011725:Pyridines; D013931:Thromboxanes; D013929:Thromboxane B2; C037787:pirmagrel; D013930:Thromboxane-A Synthase