Increased lipopolysaccharide-induced tissue factor activity and tumour necrosis factor production in monocytes after intake of aspirin: possible role of prostaglandin E2.
To determine how aspirin intake might influence lipopolysaccharide (LPS)-induced tissue factor (TF) activity and tumour necrosis factor (TNF) in human blood monocytes, we collected blood before and at various times after intake of 300 mg aspirin in 25 healthy volunteers. Aspirin intake reduced LPS-induced thromboxane B2 and PGE2 production in whole blood by 50% and 65% respectively, measured 1 h after aspirin intake. Subsequently, a 95% rise in LPS-induced TF activity in monocytes was seen as compared to a 26% rise in TNF. The rise in TF activity was maximal within 1 h after aspirin intake and no further rise was observed 3, 4 or 24 h after aspirin intake. In contrast, TF activity induced by incubating whole blood in the absence of LPS fell rapidly after the intake of aspirin. In separate experiments, a dose-dependent inhibition by PGE2 was observed in LPS-induced TF activity in monocytes. It is proposed that the increased LPS-induced TF activity and TNF production following aspirin intake may be due to suppressed PGE2 formation. The more pronounced rise in TF activity compared to TNF production may be due to an enhancement of the platelet lipoxygenase pathway that has been shown to be important for LPS-induced TF activity in monocytes.
Osterud
B
B
Institute of Medical Biology, University of Tromsø, Norway.
Olsen
J O
JO
Wilsgård
L
L
D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D015232:Dinoprostone / Q000032:analysis*; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D013925:Thromboplastin / Q000032:analysis*; D013929:Thromboxane B2 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D013925:Thromboplastin; D015232:Dinoprostone; D001241:Aspirin