Leukotriene D4 receptor blockade inhibits the immediate and late bronchoconstrictor responses to inhaled antigen in patients with asthma.J Allergy Clin Immunol. 1992 Aug; 90(2):193-201.JA
We have tested the hypothesis that leukotriene D4 (LTD4) receptor activation is involved in the development of antigen-induced bronchoconstriction. In two studies, patients with asthma received infusions of placebo or MK-571, a potent and specific LTD4 receptor antagonist (450 mg or 37.5 mg total dose, respectively). Antigen was inhaled during test-drug administration, and FEV1 was measured for 10 hours after challenge. Urine samples were collected for measurement of LTE4; plasma samples were drawn repeatedly for assay of MK-571. MK-571 infusions inhibited both immediate (0 to 3 hours) and late (3 to 10 hours) asthmatic responses. For the high MK-571 dose, the extent of inhibition, as assessed by the area under the curve of FEV1 versus time was 88% (p = 0.01) and 63% (p = 0.01), for immediate and late responses, respectively. The low MK-571 dose also inhibited both responses but to a minor extent. Mean urinary LTE4 excretion was elevated after antigen challenge and was unaffected by administration of the LTD4 receptor antagonist. The present study demonstrates that MK-571 inhibits antigen-induced asthma in a dose-related fashion; it had not effect on antigen-induced increases in urinary LTE4 excretions. The results suggest that LTD4 receptor activation plays an important role in antigen-induced asthma.