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TRP X11 Interleukin-6 in Venous Thrombosis

Funding period: 01.09.2015 – 31.08.2017

CV Karbach (Pdf, 88,6 KB)

Research funding

  • BMBF (TRP X11)
  • DFG (KA 4035/1-1)
  • Boehringer Ingelheim Foundation (Novel and neglected cardiovascular risk factors, Project 3)

Project Summary

Inflammation and increased coagulability are associated. Patients with acute or chronic inflammatory diseases more often suffer from thromboembolic events compared to healthy individuals. A crosstalk between monocytes, neutrophils, and platelets was described to be relevant in the initiation and amplification of deep vein thrombosis (DVT) (1). The development of arterial thrombosis has been reported to be accelerated by macrophages secreting the cytokine interleukine-6 (IL-6) after exposition to particulate matter leading to reduced clotting time and intravascular coagulation in tissue factor (TF) -driven thrombosis models(2). This main neutrophil-stimulating cytokine, which is produced by monocytes, macrophages, fibroblasts, endothelial cells and partially neutrophils, plays a decisive role in linking inflammation, coagulation and thrombosis. With the work proposed here, we would like to test whether IL-6, when overexpressed by myelomonocytic cells, leads to an increased thrombus formation and, vice versa, if there is less thrombus formation in mice where the myelomonocytic cells cannot respond to IL-6. Furthermore, we plan to investigate if anti-IL6 treatment leads to a reduced thrombus formation and attenuated platelet activation. Since IL-6 acts on platelets mainly via transsignaling (alternative IL-6 pathway) (3-5), we would like to evaluate if there is less thrombus formation in mice devoid of this alternative pathway. Better understanding of the role of IL-6 signaling in the interplay between monocytes/macrophages, neutrophil granulocytes and platelets could pave the way for better therapeutic options to avoid development, recurrence and chronification of thrombosis.

Principle Investigator

PD Dr. med.  Susanne Karbach, MD
PD Dr. med.  Susanne Karbach, MD
Funktionen Physician Cardiology I, Scientist, Group Leader