title: Anticoagulant properties of the anti-inflammatory cytokine IL-10 in a factor Xa-activated human monocyte model.
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 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unité de recherche des maladies hématologiques et auto-immunes, faculté de pharmacie, 5000 Monastir, Tunisie.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ben-Hadj-Khalifa
authors.forename: Philippe
authors.initials: P
authors.lastname: Nguyen
authors.forename: Touhami
authors.initials: T
authors.lastname: Mahjoub
authors.forename: Nathalie
authors.initials: N
authors.lastname: Hézard
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000906:Antibodies / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology*; D015951:Factor Xa / Q000378:metabolism*; D065427:Factor Xa Inhibitors; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D012333:RNA, Messenger; D016753:Interleukin-10; D013925:Thromboplastin; D013917:Thrombin; D015951:Factor Xa