Release of cysteinyl leukotrienes with aspirin stimulation and the effect of prostaglandin E2 on this release from peripheral blood leucocytes in aspirin-induced asthmatic patients.
Celik, G.; Bavbek, S.; Misirligil, Z.; Melli, M. 1
[Article]
Clinical & Experimental Allergy.
31(10):1615-1622, October 2001.
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Background: The decrease in prostaglandin E2 (PGE2) release due to aspirin (ASA)-induced cyclooxygenase inhibition and the increment in cysteinyl leukotriene (Cys-LT) release secondary to the removal of the inhibitory effect of PGE2 on Cys-LT release have been suggested in the pathogenesis of aspirin-induced asthma (AIA).
Objective: In this study, we aimed to investigate the in vitro release of Cys-LT and to determine the effect of PGE2 on Cys-LT release from peripheral blood leucocytes of patients with AIA after stimulation by ASA.
Patients and methods: Patients with AIA (n = 13), patients with ASA-tolerant asthma (ATA) (n = 12) and healthy volunteers as controls (n = 13) were included to the study. ASA and PGE2 at three different concentrations were applied to the peripheral blood leucocytes of the study group, and Cys-LT levels following stimulants were assessed by enzyme immunoassay method.
Results: There was no difference in baseline Cys-LT levels between groups (AIA 353.4 /- 55.5 pg/mL, ATA 354.7 /- 40.3 pg/mL, and control group 368.5 /- 30.2 pg/mL;P > 0.05). Though not present in other groups, the Cys-LT level of 453.6 /- 70.0 pg/mL following ASA stimulation was higher than baseline in patients with AIA (P = 0.04). When PGE2 was added to the ASA-stimulated samples of patients with AIA, Cys-LT levels were measured as 298.7 /- 78.6 pg/mL, 279.8 /- 79.9 pg/mL, and 243.4 /- 51.3 pg/mL at PGE2 10-7 M, 10-6 M and 10-5 M concentrations, respectively. These levels were lower than the ASA-stimulated Cys-LT values (P = 0.03, P = 0.01 and P = 0.01, respectively). The inhibitory effect of different PGE2 concentrations on Cys-LT release was also present in patients with ATA and in controls.
Conclusion: The increase in Cys-LT levels following ASA stimulation seems to be unique to AIA, which was not present in patients with ATA and in healthy controls. The inhibitory effect of PGE2 on stimulated Cys-LT levels is another important finding to elucidate the role of PGE2 in the pathogenesis of AIA.
(C) 2001 Blackwell Science Ltd.