Aspirin-Induced COX-2 Overexpression in Monocytes of Aspirin-Intolerant Patients

Abstract

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 antiCOX-2 antibodies. Enzyme up-regulation was monitored after in vitrostimulation 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.