IL-6 does not appear to mediate early-phase lipopolysaccharide-induced coagulation activation in humans.

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Summary.  Objective: Tissue factor (TF) plays a central role during disseminated intravascular coagulation (DIC) in sepsis. We hypothesized that a frequent D/I polymorphism, at nucleotide position −1208 in the promoter region, could influence TF‐mRNA and downstream coagulation. Methods: Basal‐ and lipopolysaccharide (LPS)‐induced TF‐mRNA expression, microparticle‐associated TF‐procoagulant activity and coagulation were determined in healthy men (n = 74) before and after endotoxin (LPS) infusion (2 ng kg−1). Basal values of TF‐mRNA ranged between 34 and >37.5 cycles. Results: Baseline TF‐mRNA levels significantly differed between genotypes: I/I carriers had almost 2‐fold higher TF‐mRNA levels compared to D/D carriers at baseline (P < 0.01). In accordance, higher levels of microparticle‐associated TF‐procoagulant activity could be seen in I/I carriers. However, the genotype did not affect basal or LPS‐induced levels of prothrombin fragment F1+2, D‐dimer or cytokines including tumor necrosis factor and interleukin‐6. Conclusion: The TF–1208 polymorphism is functional in that it regulates basal TF‐mRNA in circulating monocytes and circulating microparticle‐associated TF‐procoagulant activity in vivo, but does not influence the relative increase in TF‐mRNA or coagulation activation during low‐grade endotoxemia.

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