title: Effect of interleukin-6 blockade on tissue factor-induced coagulation in human endotoxemia.
abstract: OBJECTIVE
  Clinical trials show that interleukin (IL)-6 represents a predictive marker in human sepsis. Furthermore, IL-6 has been proposed as a candidate mediator for endotoxin (lipopolysaccharide)-induced coagulation activation: In a primate model, an (alphaIL-6 antibody (alphaIL-6 Ab) almost abolished lipopolysaccharide-induced coagulation activation. Therefore, we wished to determine if an alphaIL-6 Ab (B-E8) may also attenuate lipopolysaccharide-induced activation of coagulation in humans.
  
  
  METHODS
  The study was a randomized, double blind, placebo-controlled parallel group trial (n = 12 per group).
  
  
  METHODS
  University medical center.
  
  
  METHODS
  Healthy volunteers.
  
  
  METHODS
  Healthy volunteers were randomized to receive either 80 mg of a monoclonal anti-IL-6 Ab (B-E8) or placebo intravenously before bolus infusion of 2 ng/kg lipopolysaccharide.
  
  
  RESULTS
  B-E8 effectively decreased IL-6 bioactivity as measured by a Bg-bioassay in vitro and concentrations of C reactive protein. However, B-E8 did not decrease lipopolysaccharide-induced tissue factor-messenger RNA transcription or plasma concentrations of downstream coagulation variables (prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, and D-dimer concentrations). Similarly, tumor necrosis factor-alpha concentrations, fibrinolytic activity (plasmin-antiplasmin complexes), endothelial activation (soluble E-selectin), and IL-10 were unaffected.
  
  
  CONCLUSIONS
  IL-6 does not appear to mediate early-phase lipopolysaccharide-induced coagulation activation in humans.
authors.affiliation: Department of Clinical Pharmacology, University of Vienna, Vienna, Austria.
authors.forename: Ulla
authors.initials: U
authors.lastname: Derhaschnig
authors.forename: Doris
authors.initials: D
authors.lastname: Bergmair
authors.forename: Claudia
authors.initials: C
authors.lastname: Marsik
authors.forename: Irene
authors.initials: I
authors.lastname: Schlifke
authors.forename: John
authors.initials: J
authors.lastname: Wijdenes
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001778:Blood Coagulation Disorders / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood / Q000187:drug effects; D019446:Endotoxemia / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000187:drug effects / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007262:Infusions, Intravenous; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D016133:Polymerase Chain Reaction; D013925:Thromboplastin / Q000187:drug effects / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D002097:C-Reactive Protein; D019040:E-Selectin; D005338:Fibrin Fibrinogen Degradation Products; D016753:Interleukin-10; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013925:Thromboplastin; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C036309:fibrin fragment D