Basic research study
From the American Venous Forum
Inflammatory cytokine levels in chronic venous insufficiency ulcer tissue before and after compression therapy

Presented at the Twentieth Annual Meeting of the American Venous Forum, Charleston, SC, February 21, 2008.
https://doi.org/10.1016/j.jvs.2008.11.049Get rights and content
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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-β1 was upregulated in ulcer tissue following compression therapy. Rapid healing ulcers had significantly higher levels of IL-1α, IL-1β, IFN-γ, IL-12p40, and granulocyte macrophage colony stimulating factor (GM-CSF) before compression therapy, and IL-1 Ra after therapy. IFN-γ 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.

Clinical Relevance

This data suggests that cytokines may provide targets in which topical therapeutic inhibition or promotion at appropriate time points in the healing process may provide novel therapeutic approaches to the healing of CVI ulcers.

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Competition of interest: none.