Inflammatory cytokine levels in chronic venous insufficiency ulcer tissue before and after compression therapy
Open accessAbstract
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.
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Recent investigations of chronic wound tissue and fluid indicate a continual competition between inflammatory and anti-inflammatory signals leading to a misbalanced environment for proper wound healing.
“Specifically, recent investigations of chronic wound tissue and fluid indicate a continual competition between inflammatory and anti-inflammatory signals leading to a misbalanced environment for proper wound healing to occur (25, 26).”
From Wound repair and regeneration: Mechanisms, signaling, and translation (2014) · cites this paper as [26]
Deregulation of key proinflammatory cytokines such as IL-1β and TNFα prolongs the inflammatory phase and delays healing.
“As a result, deregulation of several key proinflammatory cytokines, such as IL-1β and tumor necrosis factor–α (TNFα), prolong the inflammatory phase and delay healing (26, 29).”
From Wound repair and regeneration: Mechanisms, signaling, and translation (2014) · cites this paper as [26]
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- Authors
- Beidler, S. K., Douillet, C. D., Berndt, D. F., Keagy, B. A., Rich, P. B., & Marston, W. A.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Marston, William A.
- Venue
- Journal of Vascular Surgery
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 49
- Issue
- 4
- Pages
- 1013-1020
- ISSN
- 0741-5214 (ISSN-L)
- PMC
- PMC4710545
- OpenAlex
- W2048226370
- Cited by
- 223
- References
- 46
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 17 · 2023: 17 · 2022: 21 · 2021: 21 · 2020: 16 · 2019: 11 · 2018: 14 · 2017: 16 · 2016: 13 · 2015: 9 · 2014: 11 · 2013: 7 · 2012: 11
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1568 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Journal of Vascular Surgery (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (5 T32GM00845013)
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Surgery › Diagnosis and Treatment of Venous Diseases
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Keywords
- chronic venous insufficiency, leg ulcers, compression therapy, inflammatory cytokines, ulcer healing, TGF-β1, interleukin-1, interferon-gamma, interleukin-1 receptor antagonist, GM-CSF, IL-12
- MeSH terms
- Adult, Aged, Chronic Disease, Female, Humans, Male, Middle Aged, Time Factors, Varicose Ulcer, Venous Insufficiency, Wound Healing, Cytokines, Treatment Outcome, Inflammation Mediators, Stockings, Compression
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