The effect of aspirin on LPS-incubation of whole blood was investigated. As
pirin induced a concentration dependent increase (2.5-5-fold at 5 mM aspiri
n) in LPS-induced appearance of TNF-alpha and fibrinopeptide A (FPA) in pla
sma, despite the concomitant increase in the inhibitory cytokine IL-10. Asp
irin substantially raised the levels of LPS-induced TF-mRNA and TNF alpha-m
RNA in monocytes isolated from whole blood. The median ratio for TF-/beta-a
ctin 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 TNF alpha/beta-actin mRNA ratios
were 1.8 +/- 0.4 and 5.5 +/- 2.7 respectively. Addition of exogenous PGE(2)
before incubation nearly abrogated the effect of aspirin on TNF-alpha, sub
stantiating the role of PGE(2) as a regulator of TNF-alpha synthesis, where
as 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.