title: Low-molecular weight and unfractionated heparins induce a downregulation of inflammation: decreased levels of proinflammatory cytokines and nuclear factor-kappaB in LPS-stimulated human monocytes.
abstract: Unfractionated heparin (UFH) and low-molecular weight heparin (LMWH) are well defined anticoagulant agents. Recent data suggest that both LMWH and UFH may also have potent anti-inflammatory properties; however, their mechanism of action responsible for the anti-inflammatory effect is not yet fully elucidated. This study was designed to assess the effect of LMWH and UFH on human monocytes production of inflammatory markers and nuclear translocation of nuclear factor (NF)-kappaB. Cultured monocytes were pretreated for 15 min with LMWH or UFH (10 microg and 1 microg/million cells) before stimulation with lipopolysaccharide (LPS) at a dose of 1 ng/million cells. Proinflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-8, IL-6 and IL-1beta release were subsequently measured by enzyme-linked immunosorbent assay at 6 h, and nuclear translocation of the proinflammatory NF-kappaB was assessed at 2 h. Treatment with pharmacological doses of LMWH and UFH significantly attenuated LPS-induced production of TNF-alpha, IL-8, IL-6 and IL-1beta as well as NF-kappaB translocation. These results indicate equivalent and significant heparin anti-inflammatory properties at low doses on monocyte-mediated immune response. The inhibition of NF-kappaB activation certainly represents one of the mechanisms by which heparin exerts its anti-inflammatory effect. LMWH and UFH therefore appear as potential therapeutic inhibitors of inflammation.
authors.affiliation: Thrombosis and Haemostasis Research Group, Institute of Molecular Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St James's Hospital, Dublin, Ireland. hocharh@tcd.ie
authors.forename: Hélène
authors.initials: H
authors.lastname: Hochart
authors.forename: P Vincent
authors.initials: PV
authors.lastname: Jenkins
authors.forename: Owen P
authors.initials: OP
authors.lastname: Smith
authors.forename: Barry
authors.initials: B
authors.lastname: White
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000276:immunology*; D015536:Down-Regulation; D004926:Escherichia coli; D006493:Heparin / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D014178:Translocation, Genetic / Q000187:drug effects
chemical_list: D000925:Anticoagulants; D016207:Cytokines; D006495:Heparin, Low-Molecular-Weight; D008070:Lipopolysaccharides; D016328:NF-kappa B; D006493:Heparin