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-alpha (TNF-alpha). 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-alpha, prostanoid E-2 (PGE(2)) and prostanoid I-2 (PGI(2)), and thromboxane A(2) (TXA(2)). TNF-alpha and prostanoids were determined by enzyme-linked immunoassays. Results: In seven subjects, TNF-alpha release in blood cultures decreased 24 h after intake of aspirin. The effect of aspirin on prostanoid release was assessed in three individuals: PGE(2) increased in all subjects, PGI(2) increased in two and remained unchanged in one, and TXA(2) 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-alpha release by aspirin, but abolished prostanoid production in all three individuals. Conclusion: The capacity of activated leukocytes to release TNF-alpha is reduced by ingestion of low-dose aspirin, independent of changes in prostanoid biosynthesis.
