@Article{ecn.2012.0315,
AUTHOR = {Sonia Ben-Hadj-Khalifa, Philippe Nguyen, Touhami Mahjoub, Nathalie Hézard},
TITLE = {Anticoagulant properties of the anti-inflammatory cytokine IL-10 in a factor Xa-activated human monocyte model},
JOURNAL = {European Cytokine Network},
VOLUME = {23},
YEAR = {2012},
NUMBER = {3},
PAGES = {87--92},
URL = {http://www.techscience.com/ECN/v23n3/65698},
ISSN = {1952-4005},
ABSTRACT = {Background: Monocytes and factor Xa (FXa) are procoagulant agents implicated in the physiopathological
processes of atherosclerosis and thrombosis.Objective: we evaluated the anticoagulant effect of the
anti-inflammatory cytokine IL-10 on an FXa-activated human monocyte (Hu-monocyte) procoagulant phenotype.Methods:
Hu-monocytes were purified by elutriation and activated by FXa. The effect of IL-10 was assessed
by means of a 2 h pre-incubation step with recombined human IL-10 (0.5 and 1 ng/mL). Real-time RT-PCR and
Western blotting were used to evaluate the effect of IL-10 on tissue factor (TF) mRNA and protein synthesis.
A thrombin generation (TG) assay was used as a functional test to assess the effect of IL-10 on TF-dependent TG.
Results: we showed that IL-10 inhibited both TF mRNA and TF protein expression in a dose-dependant manner. We
showed, as a functional consequence, that IL-10 inhibited Hu-monocyte-triggered TG and that this inhibition was
concentration-dependant, and significant for all TG phases. The rate index of the propagation phase (rate index)
was the most sensitive parameter while the endpoint of TG decay (S-tail) and the endogenous thrombin potential
(ETP) were the least sensitive (inhibition of 80, 40 and 30% respectively). The IL-10 pattern of TG inhibition was
similar to TF-Ab-induced inhibition: IC<sub>50</sub> were not reached by ETP and S-tail, and the lowest IC<sub>50</sub> values were
reached by the rate index (0.61 ± 0.12 ng/mL and 1.87 ± 0.35 μg/mL respectively).Conclusion: the anticoagulant
effect of the anti-inflammatory cytokine IL-10 in an FXa-activated Hu-monocyte model is an additional illustration
of the cross-talk between inflammation and coagulation, opening new approaches in the field of arteriosclerosis and
thrombosis.},
DOI = {10.1684/ecn.2012.0315}
}