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.

Abstract

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.

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 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.

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 PGE(2) on stimulated Cys-LT levels is another important finding to elucidate the role of PGE(2) in the pathogenesis of AIA.

• Authors: G Celik, S Bavbek, Z Misirligil, M Melli
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 31 Issue 10 Pg. 1615-22 (Oct 2001) ISSN: 0954-7894 [Print] England
• PMID: 11678863 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Leukotrienes
• cysteinyl-leukotriene
• Cytochalasin B
• N-Formylmethionine Leucyl-Phenylalanine
• Dinoprostone
• Cysteine
• Aspirin

Topics

• Adult
• Aged
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects, pharmacology)
• Aspirin (adverse effects, pharmacology)
• Asthma (chemically induced, metabolism)
• Cysteine (drug effects, metabolism)
• Cytochalasin B (pharmacology)
• Dinoprostone (pharmacology)
• Female
• Humans
• Leukocytes (drug effects, metabolism)
• Leukotrienes (metabolism)
• Male
• N-Formylmethionine Leucyl-Phenylalanine (pharmacology)
• Stimulation, Chemical