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

• Published in: European cytokine network Vol. 23; no. 3; p. 87
• Main Authors: Ben-Hadj-Khalifa, Sonia, Nguyen, Philippe, Mahjoub, Touhami, Hézard, Nathalie
• Format: Journal Article
• Language: English
• Published: France 01-07-2012
• Subjects: Adult; Anti-Inflammatory Agents - pharmacology; Antibodies - pharmacology; Anticoagulants - pharmacology; Factor Xa - metabolism; Factor Xa Inhibitors; Humans; Interleukin-10 - pharmacology; Models, Biological; Monocytes - drug effects; Monocytes - metabolism; Phenotype; RNA, Messenger - genetics; RNA, Messenger - metabolism; Thrombin - metabolism; Thromboplastin - genetics; Thromboplastin - immunology; Thromboplastin - metabolism
• ISSN: 1952-4005
• DOI: 10.1684/ecn.2012.0315

Monocytes and factor Xa (FXa) are procoagulant agents implicated in the physiopathological processes of atherosclerosis and thrombosis.
we evaluated the anticoagulant effect of the anti-inflammatory cytokine IL-10 on an FXa-activated human monocyte (Hu-monocyte) procoagulant phenotype.
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.
we showed that IL-10 inhibited both TFmRNA 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(50) were not reached by ETP and S-tail, and the lowest IC(50) values were reached by the rate index (0.61 ± 0.12 ng/mL and 1.87 ± 0.35 μg/mL respectively).
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.