Aspirin potentiates LPS-induced fibrin formation (FPA) and TNF-alpha-synthesis in whole blood.
The effect of aspirin on LPS-incubation of whole blood was investigated. Aspirin induced a concentration dependent increase (2.5-5-fold at 5 mM aspirin) in LPS-induced appearance of TNF-alpha and fibrinopeptide A (FPA) in plasma, despite the concomitant increase in the inhibitory cytokine IL-100. Aspirin substantially raised the levels of LPS-induced TF-mRNA and TNFalpha-mRNA in monocytes isolated from whole blood. The median ratio for TF-/beta-actin mRNA increased from 1.5 +/- 0.44 in the presence of LPS-alone, to 2.5 +/- 0.51 when 5 mM aspirin was added. The TNFalpha/beta-actin mRNA ratios were 1.8 +/- 0.4 and 5.5 +/- 2.7 respectively. Addition of exogenous PGE2 before incubation nearly abrogated the effect of aspirin on TNF-alpha, substantiating the role of PGE2 as a regulator of TNF-alpha synthesis, whereas the effect on FPA was small. Thus, in the presence of LPS in this whole blood model, aspirin apparently had a pro-inflammatory rather than an anti-inflammatory effect.
Osnes
L T
LT
Dept. of Clinical Chemistry, Ullevaal University Hospital, Oslo, Norway.
Haug
K B
KB
Joø
G B
GB
Westvik
A B
AB
Ovstebø
R
R
Kierulf
P
P
D001241:Aspirin / Q000494:pharmacology*; D001773:Blood Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000096:biosynthesis* / Q000187:drug effects; D005344:Fibrinopeptide A / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000096:biosynthesis / Q000187:drug effects; D011516:Prothrombin / Q000096:biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000097:blood / Q000187:drug effects; D013925:Thromboplastin / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics
D008070:Lipopolysaccharides; D010446:Peptide Fragments; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C045879:prothrombin fragment 1.2; D016753:Interleukin-10; D005344:Fibrinopeptide A; D011516:Prothrombin; D005337:Fibrin; D013925:Thromboplastin; D015232:Dinoprostone; D001241:Aspirin