DOI: 10.1097/01.CCM.0000126265.08175.BE
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PMID: 15190963
Issn Print: 0090-3493
Publication Date: 2004/05/01
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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 αIL-6 antibody (αIL-6 Ab) almost abolished lipopolysaccharide-induced coagulation activation. Therefore, we wished to determine if an αIL-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 B9-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-α 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.
