Inflammatory cytokine levels in chronic venous insufficiency ulcer tissue before and after compression therapy

J Vasc Surg. 2009 Apr;49(4):1013-20. doi: 10.1016/j.jvs.2008.11.049.


Objective: Elevated inflammatory cytokine levels have been implicated in the pathogenesis of non-healing chronic venous insufficiency (CVI) ulcers. The goal of this study was to determine the protein levels of a wide range of inflammatory cytokines in untreated CVI ulcer tissue before and after 4 weeks of high-strength compression therapy. These levels were compared to cytokines present in healthy tissue.

Methods: Thirty limbs with untreated CVI and leg ulceration received therapy for 4 weeks with sustained high-compression bandaging at an ambulatory wound center. Biopsies were obtained from healthy and ulcerated tissue before and after therapy. A multiplexed protein assay was used to measure multiple cytokines in a single sample. Patients were designated as rapid or delayed healers based on ulcer surface area change.

Results: The majority of pro-inflammatory cytokine protein levels were elevated in ulcer tissue compared to healthy tissue, and compression therapy significantly reduced these cytokines. TGF-beta1 was upregulated in ulcer tissue following compression therapy. Rapid healing ulcers had significantly higher levels of IL-1alpha, IL-1beta, IFN-gamma, IL-12p40, and granulocyte macrophage colony stimulating factor (GM-CSF) before compression therapy, and IL-1 Ra after therapy. IFN-gamma levels significantly decreased following therapy in the rapidly healing patients.

Conclusion: CVI ulcer healing is associated with a pro-inflammatory environment prior to treatment that reflects metabolically active peri-wound tissue that has the potential to heal. Treatment with compression therapy results in healing that is coupled with reduced pro-inflammatory cytokine levels and higher levels of the anti-inflammatory cytokine IL-1 Ra.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Chronic Disease
  • Cytokines / blood*
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Male
  • Middle Aged
  • Stockings, Compression*
  • Time Factors
  • Treatment Outcome
  • Varicose Ulcer / immunology
  • Varicose Ulcer / physiopathology
  • Varicose Ulcer / therapy*
  • Venous Insufficiency / immunology
  • Venous Insufficiency / physiopathology
  • Venous Insufficiency / therapy*
  • Wound Healing*


  • Cytokines
  • Inflammation Mediators