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

Ilse Beckmann ； Shlomo Ben-Efraim ； Monica Vervoort ； Henk C. S. Wallenburg

《Mediators of Inflammation》 2001卷 (2001/12) Pp. 81-88

https://doi.org/10.1080/09629350120054554

摘要

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-a (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 E_2 (PGE_2) and prostanoid I_2 (PGI_2 ), and thromboxane A_2 (TXA_2 ). TNF-a and prostanoids were determined by enzyme-linked immunoassays. Results: In seven subjects, TNF-αrelease 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.

關鍵字

Low-dose aspirin ； Tumor necrosis factor-a ； Cyclooxygenase inhibition ； Prostanoids