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. DESIGN: The study was a randomized, double blind, placebo-controlled parallel group trial (n = 12 per group). SETTING:University medical center. PATIENTS: Healthy volunteers. INTERVENTIONS: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. MEASUREMENTS AND MAIN 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. CONCLUSION: IL-6 does not appear to mediate early-phase lipopolysaccharide-induced coagulation activation in humans.
RCT Entities:
OBJECTIVE: Clinical trials show that interleukin (IL)-6 represents a predictive marker in humansepsis. 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. DESIGN: The study was a randomized, double blind, placebo-controlled parallel group trial (n = 12 per group). SETTING: University medical center. PATIENTS: Healthy volunteers. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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. CONCLUSION:IL-6 does not appear to mediate early-phase lipopolysaccharide-induced coagulation activation in humans.
Authors: P Opfermann; U Derhaschnig; A Felli; J Wenisch; D Santer; A Zuckermann; M Dworschak; B Jilma; B Steinlechner Journal: Clin Exp Immunol Date: 2015-04 Impact factor: 4.330
Authors: Christoph Schriefl; Christian Schoergenhofer; Michael Poppe; Christian Clodi; Matthias Mueller; Florian Ettl; Bernd Jilma; Juergen Grafeneder; Michael Schwameis; Heidrun Losert; Michael Holzer; Fritz Sterz; Andrea Zeiner-Schatzl Journal: Sci Rep Date: 2021-05-13 Impact factor: 4.379