Aspirin-induced COX-2 overexpression in monocytes of aspirin-intolerant patients.
BACKGROUND
We hypothesize that alternate regulation of cyclooxygenase-2 (COX-2) may predispose patients to aspirin-induced exacerbations.Therefore, we want to examine the dynamics of COX-2 up-regulation in whole blood monocytes in the presence and absence of aspirin.


METHODS
COX-2 expression was evaluated by flow cytometry through intracellular staining of whole blood monocytes with anti-COX-2 antibodies. Enzyme up-regulation was monitored after in vitro stimulation with lipopolysaccharide (LPS) and/or aspirin in 19 aspirin-intolerant (AI) patients (8 aspirin-sensitive asthmatics and 11 urticaria-angioedema patients) and 14 healthy controls.


RESULTS
We found significantly higher COX-2 expression levels after stimulation with LPS and aspirin (mean 78.8, range 44.9-92.3; p = 0.0002) in comparison to LPS alone (mean 65.9%, range 33.6-82.6) in AI patients. A comparable, but lower up-regulation was also observed after aspirin stimulation alone (median 2.1%, range 0.5-15.9; p = 0.004) in comparison with baseline values (median 1%, range 0.1-5.4). There was no significant difference in COX-2 expression between LPS and aspirin stimulation (mean 61.8%, range 26.8-89.2; p = 0.09) and LPS stimulation (mean 55.5%, range 28.1-74.3) nor between aspirin stimulation alone (median 0.5%, range 0-8.6; p = 0.8) and baseline values (median 0.4%, range 0-5.4) in healthy control subjects.


CONCLUSIONS
The main finding of this study is that COX-2 appears to be differentially regulated in aspirin-sensitive patients. What is really new is the observation that aspirin and LPS increase COX-2 expression on blood monocytes of AI asthmatics, a finding in contrast with the lack of an effect of the same stimuli on COX-2 expression on monocytes from healthy subjects.
Morgan
Tina
T
University Clinic of Respiratory and Allergic Diseases, SI-4204 Golnik, Slovenia.
Bajrovic
Nissera
N
Silar
Mira
M
Kosnik
Mitja
M
Korosec
Peter
P
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D001241:Aspirin / Q000009:adverse effects* / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced* / Q000201:enzymology* / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004342:Drug Hypersensitivity / Q000201:enzymology*; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D015854:Up-Regulation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D001241:Aspirin