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

2009; Elsevier BV; Volume: 49; Issue: 4 Linguagem: Inglês

10.1016/j.jvs.2008.11.049

1097-6809

Stephanie K. Beidler, Christelle Douillet, Daniel Berndt, Blair A. Keagy, Preston B. Rich, William A. Marston,

Peripheral Artery Disease Management

ObjectiveElevated 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.MethodsThirty 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.ResultsThe 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.ConclusionCVI 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. 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. 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. 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. 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.