Release of cysteinyl leukotrienes with aspirin stimulation and the effect of prostaglandin E(2) on this release from peripheral blood leucocytes in aspirin-induced asthmatic patients.
BACKGROUND
The decrease in prostaglandin E(2) (PGE(2)) 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 PGE(2) 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 PGE(2) on Cys-LT release from peripheral blood leucocytes of patients with AIA after stimulation by ASA.


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 PGE(2) 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 PGE(2) 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 PGE(2) concentrations on Cys-LT release was also present in patients with ATA and in controls.


CONCLUSIONS
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 PGE(2) on stimulated Cys-LT levels is another important finding to elucidate the role of PGE(2) in the pathogenesis of AIA.
Celik
G
G
Department of Chest Diseases, Division of Allergic Diseases, Ankara University School of Medicine, Ankara, Turkey. fcelik@dialup.ankara.edu.tr
Bavbek
S
S
Misirligil
Z
Z
Melli
M
M
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology*; D001241:Aspirin / Q000009:adverse effects* / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced* / Q000378:metabolism*; D003545:Cysteine / Q000187:drug effects* / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism*; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D013268:Stimulation, Chemical
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015232:Dinoprostone; D003545:Cysteine; D001241:Aspirin