title: 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.
  
  
  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.
authors.affiliation: Department of Chest Diseases, Division of Allergic Diseases, Ankara University School of Medicine, Ankara, Turkey. fcelik@dialup.ankara.edu.tr
authors.forename: G
authors.initials: G
authors.lastname: Celik
authors.forename: S
authors.initials: S
authors.lastname: Bavbek
authors.forename: Z
authors.initials: Z
authors.lastname: Misirligil
authors.forename: M
authors.initials: M
authors.lastname: Melli
mesh_terms: 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
chemical_list: 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