title: IL-10 modulates fondaparinux inhibition of monocyte-induced thrombin generation.
abstract: In addition to its established immuno-regulating capacity, the anti-inflammatory cytokine interleukin (IL)-10 exerts direct effects on coagulation. IL-10 down regulates the expression of tissue factor (TF) and thrombin generation (TG). Thus, we hypothesised that IL-10 could enhance the effect of anticoagulants. To evaluate in vitro the potential additive effect of IL-10 on fondaparinux-induced anticoagulation. Human monocytes were purified by elutriation, and were activated by factor Xa (FXa). Real-time RT-PCR and Western blotting were used to evaluate FXa-induced TF synthesis. TG test was used as a functional test to assess TF-dependent monocyte procoagulation, and to evaluate the effects of IL-10 (200 and 500 pg/ml) and fondaparinux (0.0, 0.1, 0.4, 0.7 and 1.2 μg/ml), separately and in combination. We confirmed that FXa induced TF mRNA and protein synthesis by monocyte in a concentration dependent manner. We showed that FXa-activated monocytes triggered TG via TF expression. We reported that IL-10 inhibited TG with a marginal effect seen at 200 pg/ml. Results with fondaparinux showed a concentration-dependent TG inhibition. The combination of IL-10 and fondaparinux effects demonstrated that IL-10: (i) potentiates the inhibitory effect of fondaparinux on TG by 10-30%, and (ii) dramatically modifies fondaparinux IC50 for each TG parameter. IL-10 enhances in vitro the extent of anticoagulation induced by fondaparinux.
authors: Faculté de Pharmacie, Unité de Recherche des Maladies Hématologiques et Auto-Immunes, Monastir, Tunisia.
authors: Sonia
authors: S
authors: Ben-Hadj-Khalifa
authors: Nathalie
authors: N
authors: Hézard
authors: Wassim Y
authors: WY
authors: Almawi
authors: Souad
authors: S
authors: Lakbakbi
authors: Catherine
authors: C
authors: Macé
authors: Pascale
authors: P
authors: Cornillet-Lefebvre
authors: Touhami
authors: T
authors: Mahjoub
authors: Philippe
authors: P
authors: Nguyen
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015951:Factor Xa / Q000494:pharmacology; D005260:Female; D000077425:Fondaparinux; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013917:Thrombin / Q000096:biosynthesis*
chemical_list: D000925:Anticoagulants; C508609:IL10 protein, human; D011134:Polysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10; D013917:Thrombin; D015951:Factor Xa; D000077425:Fondaparinux