Release of tumor necrosis factor-α and prostanoids in whole blood cultures after in vivo exposure to low-dose aspirin

Abstract

Background: The preventive effect of low-dose aspirin in cardiovascular disease is generally attributed to its antiplatelet action caused by differential inhibition of platelet cyclooxygenase-1. However, there is evidence that aspirin also affects release of inflammatory cytokines, including tumor necrosis factor-α (TNF-α). It is not known whether this is caused by direct action on the cytokine pathway or indirectly through cyclooxygenase inhibition and altered prostanoid synthesis, or both. Methods: We assessed the capacity of lipopolysaccharide-activated leukocytes in whole blood cultures of eight healthy subjects following a single oral dose of 80 mg aspirin to release TNF-α, prostanoid E2 (PGE2) and prostanoid I2 (PGI2), and thromboxane A2 (TXA2). TNF-α and prostanoids were determined by enzyme-linked immunoassays. Results: In seven subjects, TNF-α release in blood cultures decreased 24 h after intake of aspirin. The effect of aspirin on prostanoid release was assessed in three individuals: PGE2 increased in all subjects, PGI2 increased in two and remained unchanged in one, and TXA2 was reduced in two and unchanged in one individual. The presence of DFU, a specific inhibitor of cyclooxygenase 2, did not affect the reduction of TNF-α release by aspirin, but abolished prostanoid production in all three individuals. Conclusion: The capacity of activated leukocytes to release TNF-α is reduced by ingestion of low-dose aspirin, independent of changes in prostanoid biosynthesis.