title: Pretreatment with a 55-kDa tumor necrosis factor receptor-immunoglobulin fusion protein attenuates activation of coagulation, but not of fibrinolysis, during lethal bacteremia in baboons.
abstract: Baboons (Papio anubis) receiving a lethal intravenous infusion with live Escherichia coli were pretreated with either a 55-kDa tumor necrosis factor (TNF) receptor-IgG fusion protein (TNFR55:IgG) (n = 4, 4.6 mg/kg) or placebo (n = 4). Neutralization of TNF activity in TNFR55:IgG-treated animals was associated with a complete prevention of mortality and a strong attenuation of coagulation activation as reflected by the plasma concentrations of thrombin-antithrombin III complexes (P < .05). Activation of fibrinolysis was not influenced by TNFR55:IgG (plasma tissue-type plasminogen activator and plasmin-alpha2-antiplasmin complexes), whereas TNFR55:IgG did inhibit the release of plasminogen activator inhibitor type I (P < .05). Furthermore, TNFR55:IgG inhibited neutrophil degranulation (plasma levels of elastase-alpha1-antitrypsin complexes, P < .05) and modestly reduced release of secretory phospholipase A2. These data suggest that endogenous TNF contributes to activation of coagulation, but not to stimulation of fibrinolysis, during severe bacteremia.
authors.affiliation: Cornell University Medical College, Laboratory of Surgical Metabolism, New York, New York, USA.
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
authors.forename: P M
authors.initials: PM
authors.lastname: Jansen
authors.forename: K J
authors.initials: KJ
authors.lastname: Van Zee
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: H A
authors.initials: HA
authors.lastname: Oldenburg
authors.forename: H
authors.initials: H
authors.lastname: Loetscher
authors.forename: W
authors.initials: W
authors.lastname: Lesslauer
authors.forename: S F
authors.initials: SF
authors.lastname: Lowry
authors.forename: L L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D016470:Bacteremia / Q000097:blood*; D001777:Blood Coagulation; D005342:Fibrinolysis; D007074:Immunoglobulin G / Q000502:physiology*; D010215:Papio; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D015703:Antigens, CD; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha