The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
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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“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]
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“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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Items 201–223 of 223
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“12,13 Approximately 48 to 72 h after an injury, monocytes migrate to the wound site and primarily differentiate into M1-type macrophages — described as “ pro-inflammatory ”— serving as the predominant cell type during the inflammatory phase of wound healing.”
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“Elevated levels of pro-inflammatory cytokines, including IL-1 β and TNF-α , further extend the inflammatory phase and delay tissue repair (Beidler et al., 2009).”
Depressed inflammatory mediators may suggest immunologic dysregulation in advanced venous disease
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Metadata
- 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 › Surgery › 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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