Alterations in tumor necrosis factor-induced endothelial cell procoagulant activity by hyperthermia

Nancy M. Carroll, Dina M. Elaraj, Markus Puhlmann, David M. Weinreich, Ewa M. Turner, Hui Xu, H. Richard Alexander*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


TNF is a cytokine with potent antitumor activity in murine models and when administered clinically via regional perfusion. There is substantial evidence that this antitumor activity depends in large part on TNF's procoagulant effect on tumor neovasculature, which is mediated by induction of endothelial cell tissue factor (TF), a component of the extrinsic clotting cascade. In regional perfusion of a cancer-bearing limb or organ, TNF is always administered under hyperthermic temperatures; however, little is known about the effect of hyperthermia on TNF-mediated procoagulant activity in endothelium. We examined the effects of hyperthermia on TNF-mediated procoagulant activity in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to TNF at normothermic (37°C) and hyperthermic (41°C) temperatures for 90 min, then assayed for clotting activity, TF protein production and mRNA production of TF and tissue factor pathway inhibitor-2 (TFPI-2), an endogenous inducible inhibitor of TF activity in HUVECs. TNF treatment at 41°C significantly reduced clotting activity, TF protein and mRNA as well as TFPI-2 mRNA compared to treatment at 37°C. These data show that hyperthermia significantly reduces the procoagulant effects of TNF on endothelial tissue compared to normothermia, which may have important clinical implications for the use of TNF in regional perfusion.

Original languageEnglish (US)
Pages (from-to)457-462
Number of pages6
JournalInternational Journal of Cancer
Issue number3
StatePublished - Sep 1 2004


  • Coagulation
  • Endothelium
  • Hyperthermia
  • Isolated limb perfusion
  • Tissue factor
  • Tissue factor pathway inhibitor-2
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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