Arachidonic acid metabolism in monocytes of aspirin-sensitive asthmatic patients before and after oral aspirin challenge.
Aspirin and nonsteroidal antiinflammatory drugs induce bronchospastic reactions in patients with aspirin-sensitive respiratory disease. Although the mechanism of this reaction is unknown, all drugs that induce the respiratory reaction also inhibit the cyclooxygenase enzyme. The ensuing changes in arachidonate metabolism are presumed to play a role in the pathogenesis of the reaction. We measured generation of leukotrienes and thromboxane by calcium ionophore stimulated blood monocytes. Before aspirin challenge, monocytes released significantly more thromboxane B2 in patients with aspirin sensitivity than in patients without aspirin sensitivity or in healthy control subjects (p < 0.02). During aspirin-induced bronchospasm, release of leukotriene B4 increased significantly (45.5%, p = 0.018), whereas release of thromboxane B2 decreased (-46.9%, p = 0.028). Two hours after ingestion of 60 mg aspirin, normal monocyte release of thromboxane B2 did not drop, whereas leukotriene B4 release increased. Monocytes formed only minimal amounts of leukotriene C4. We conclude that the profile of released eicosanoids from aspirin-sensitive monocytes is distinct from non-aspirin-sensitive subjects, and that these differences could contribute to the development of bronchospasm after aspirin ingestion.
Juergens
U R
UR
Molecular and Experimental Medicine Research Institute Scripps Clinic, La Jolla, CA.
Christiansen
S C
SC
Stevenson
D D
DD
Zuraw
B L
BL
D000284:Administration, Oral; D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism*; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000378:metabolism*; D001986:Bronchial Spasm / Q000139:chemically induced; D000001:Calcimycin / Q000494:pharmacology; D015777:Eicosanoids / Q000378:metabolism; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism
D015777:Eicosanoids; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; D013929:Thromboxane B2; D001241:Aspirin