Open Access

ARTICLE

Anticoagulant properties of the anti-inflammatory cytokine IL-10 in a factor Xa-activated human monocyte model

Sonia Ben-Hadj-Khalifa^1,2, Philippe Nguyen^2,3, Touhami Mahjoub¹, Nathalie Hézard^2,3

1 Unité de recherche des maladies hématologiques et auto-immunes, faculté de pharmacie, 5000 Monastir, Tunisie
2 Laboratoire d’hématologie, CHU Robert Debré, 51092 Reims Cedex, France
3 EA-3801, Faculté de Médecine, Université Reims-Champagne Ardenne, 51100 Reims Cedex, France

* Corresponding Author: N. Hézard,

European Cytokine Network 2012, 23(3), 87-92. https://doi.org/10.1684/ecn.2012.0315

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: IC₅₀ were not reached by ETP and S-tail, and the lowest IC₅₀ 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.

---

Keywords

---