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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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Cites
Measurement of protein using bicinchoninic acid
Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J., & Klenk, D. C. (1985) · Analytical Biochemistry · doi:10.1016/0003-2697(85)90442-7 · Cited by 18,482
Points of control in inflammation
Nathan, C. (2002) · Nature · doi:10.1038/nature01320 · Cited by 2,738
Resolution of inflammation: the beginning programs the end
Serhan, C. N., & Savill, J. (2005) · Nature Immunology · doi:10.1038/ni1276 · Cited by 2,552
The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum.
(1975) · PubMed Central · Cited by 1,437
Compression for venous leg ulcers
O’Meara, S., Cullum, N. A., Nelson, E. A., & Dumville, J. C. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd000265.pub3 · Cited by 936
PDGF and FGF stimulate wound healing in the genetically diabetic mouse.
Greenhalgh, D. G., Sprugel, K. H., Murray, M. J., & Ross, R. (1990) · Europe PMC (PubMed Central) · Cited by 681
Hübner, G., Brauchle, M. A., Smola, H., Madlener, M., Fässler, R., & Werner, S. (1996) · Cytokine · doi:10.1006/cyto.1996.0074 · Cited by 499
Definition of venous reflux in lower-extremity veins
Labropoulos, N., Tiongson, J. E., Pryor, L., Tassiopoulos, A. K., Kang, S. S., Mansour, M., & Baker, W. H. (2003) · Journal of Vascular Surgery · doi:10.1016/s0741-5214(03)00424-5 · Cited by 469
Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers
Trengove, N. J., Bielefeldt‐Ohmann, H., & Stacey, M. C. (2000) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2000.00013.x · Cited by 432
Simultaneous quantitation of 15 cytokines using a multiplexed flow cytometric assay
Carson, R. T., & Vignali, D. A. A. (1999) · Journal of Immunological Methods · doi:10.1016/s0022-1759(99)00069-1 · Cited by 404
Radstake, T. R. D. J., Roelofs, M. F., Bastiaansen-Jenniskens, Y. M., Oppers‐Walgreen, B., van Riel, P. L. C. M., Barrera, P., Joosten, L. A. B., & van den Berg, W. B. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20678 · Cited by 331
duPont, N. C., Wang, K., Wadhwa, P. D., Culhane, J. F., & Nelson, E. L. (2005) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2005.03.005 · Cited by 325
Arterial Inflammation in Mice Lacking the Interleukin 1 Receptor Antagonist Gene
Nicklin, M. J. H., Hughes, D. E., Barton, J. L., Ure, J. M., & Duff, G. W. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.2.303 · Cited by 319
Compression for preventing recurrence of venous ulcers
Nelson, E. A., Bell-Syer, S. E., Cullum, N. A., & Webster, J. (2000) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002303 · Cited by 312
Compression for venous leg ulcers
Cullum, N. A., Nelson, E. A., Fletcher, A., & Sheldon, T. (2001) · doi:10.1002/14651858.cd000265 · Cited by 306
Fifteen-year results of ambulatory compression therapy for chronic venous ulcers.
Mayberry, J. C., Moneta, G. L., Taylor, L. M., & Porter, J. M. (1991) · PubMed · Cited by 263
Oxidative stress in chronic venous leg ulcers
Wlaschek, M., & Scharffetter‐Kochanek, K. (2005) · Wound Repair and Regeneration · doi:10.1111/j.1067-1927.2005.00065.x · Cited by 241
Kantor, J., & Margolis, D. J. (2000) · British Journal of Dermatology · doi:10.1046/j.1365-2133.2000.03478.x · Cited by 233
Prognostic indicators in venous ulcers
Phillips, T. J., Machado, F., Trout, R., Porter, J., Olin, J. W., & Falanga, V. (2000) · Journal of the American Academy of Dermatology · doi:10.1067/mjd.2000.107496 · Cited by 217
Marston, W. A., Carlin, R. E., Passman, M. A., Farber, M. A., & Keagy, B. A. (1999) · Journal of Vascular Surgery · doi:10.1016/s0741-5214(99)70076-5 · Cited by 196
Self-citationSimultaneous quantification of proinflammatory cytokines in human plasma using the LabMAP™ assay
Prabhakar, U., Eirikis, E., & Davis, H. M. (2002) · Journal of Immunological Methods · doi:10.1016/s0022-1759(01)00543-9 · Cited by 185
Erickson, C. A., Lanza, D. J., Karp, D. L., Edwards, J. W., Seabrook, G. R., Cambria, R. A., Freischlag, J. A., & Towne, J. B. (1995) · Journal of Vascular Surgery · doi:10.1016/s0741-5214(95)70051-x · Cited by 178
Delayed Wound Healing in the Absence of Intercellular Adhesion Molecule-1 or L-Selectin Expression
Nagaoka, T., Kaburagi, Y., Hamaguchi, Y., Hasegawa, M., Takehara, K., Steeber, D. A., Tedder, T. F., & Sato, S. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64534-8 · Cited by 172
Fürst, D. E. (2004) · Clinical Therapeutics · doi:10.1016/j.clinthera.2004.12.019 · Cited by 172
Validation of venous leg ulcer guidelines in the United States and United Kingdom
McGuckin, M., Waterman, R. P., Brooks, J., Cherry, G. W., Porten, L., Hurley, S., & Kerstein, M. D. (2002) · The American Journal of Surgery · doi:10.1016/s0002-9610(01)00856-x · Cited by 145
The role of air plethysmography in the diagnosis of chronic venous insufficiency
Criado, E., Farber, M. A., Marston, W. A., Daniel, P. F., Burnham, C. B., & Keagy, B. A. (1998) · Journal of Vascular Surgery · doi:10.1016/s0741-5214(98)70231-9 · Cited by 145
Self-citationRAY, C. A., Bowsher, R. R., Smith, W. C., Devanarayan, V., Willey, M. B., Brandt, J. T., & Dean, R. A. (2004) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2004.05.024 · Cited by 133
Chen, W. Y. J., & Rogers, A. A. (2007) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2007.00250.x · Cited by 133
Beidler, S. K., Douillet, C., Berndt, D., Keagy, B. A., Rich, P. B., & Marston, W. A. (2008) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2008.00415.x · Cited by 130
Self-citationThe influence of wound geometry on the measurement of wound healing rates in clinical trials
Gorin, D. R., Cordts, P. R., LaMorte, W. W., & Menzoı́an, J. O. (1996) · Journal of Vascular Surgery · doi:10.1016/s0741-5214(96)80021-8 · Cited by 117
Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome
Natelson, B. H., Weaver, S., Tseng, C., & Ottenweller, J. E. (2005) · Clinical and Vaccine Immunology · doi:10.1128/cdli.12.1.52-55.2005 · Cited by 113
Franks, P. J., & Moffatt, C. J. (2001) · Quality of Life Research · doi:10.1023/a:1013825924765 · Cited by 112
Pappas, P. J., You, R., Rameshwar, P., Gorti, R., DeFouw, D. O., Phillips, C. K., Padberg, F. T., Silva, M., Simonian, G. T., Hobson, R. W., et al. (1999) · Journal of Vascular Surgery · doi:10.1016/s0741-5214(99)70054-6 · Cited by 97
Compression for preventing recurrence of venous ulcers
Nelson, Bell-Syer, & Cullum (2000) · Cited by 86
Interleukin-1α and Collagenase Activity Are Elevated in Chronic Wounds
Barone, E. J., Yager, D. R., Pozez, A. L., Olutoye, O. O., Crossland, M. C., Diegelmann, R. F., & Cohen, I. K. (1998) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-199809040-00015 · Cited by 80
Banno, T., Adachi, M., Mukkamala, L., & Blumenberg, M. (2003) · Antiviral Therapy · doi:10.1177/135965350300800616 · Cited by 72
Konur, A., Schulz, U., Eißner, G., Andreesen, R., & Holler, E. (2005) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2005.06508.x · Cited by 62
Interleukin-1α and Collagenase Activity Are Elevated in Chronic Wounds
Barone, E. J., Yager, D. R., Pozez, A. L., Olutoye, O. O., Crossland, M. C., Diegelmann, R. F., & Cohen, K. I. (1998) · Plastic and Reconstructive Surgery · doi:10.1097/00006534-199809020-00015 · Cited by 62 · cited 1×
“IL-1 is a pleiotropic cytokine, and previous studies have reported that IL-1 is present in lower levels in acute wound fluid when compared to fluid from chronic wounds.(30) In our study, treatment of CVI ulcers with 4 weeks of compression therapy resulted in a decrease in the levels of the majority of the pro-inflamma…”
ResultLal, B. K., Saitô, S., Pappas, P. J., Padberg, F. T., Cerveira, J. J., Hobson, R. W., & Durán, W. N. (2003) · Journal of Vascular Surgery · doi:10.1016/s0741-5214(02)75295-6 · Cited by 58
Buttmann, M., Goebeler, M., Toksoy, A., Schmid, S., Graf, W., Berberich‐Siebelt, F., & Rieckmann, P. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.07.011 · Cited by 51
Systemic Administration of Interferon-γ Impairs Wound Healing
Miles, R. H., Paxton, T. P., Zacheis, D., Dries, D. J., & Gamelli, R. L. (1994) · Journal of Surgical Research · doi:10.1006/jsre.1994.1045 · Cited by 42
Management and prevention of venous leg ulcers: a literature-guided approach.
Kunimoto, B. (2001) · PubMed · Cited by 28
EFFECTS OF INTERFERONS ON TUMOUR NECROSIS FACTOR α PRODUCTION FROM HUMAN KERATINOCYTES
Matsuura, K., Otsuka, F., & Fujisawa, H. (1998) · Cytokine · doi:10.1006/cyto.1997.0326 · Cited by 22
Özden, M. G., Erel, A., Erdem, Ö., & Öztaş, M. (2004) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/j.1468-3083.2004.01086.x · Cited by 15
A potential role of interferon-γ in the pathogenesis of venous leg ulcers
Simka, M. (2006) · Medical Hypotheses · doi:10.1016/j.mehy.2005.12.031 · Cited by 8
Research works printed but not linked: 1
- Leibovich, 1975, The role of the macrophage in wound repair, Am J Pathol, 78, 71
Cited by
Sorted by citations
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Eming, S. A., Martin, P., & Tomic-Canic, M. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009337 · Cited by 3,562
“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).”
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“tumor necrosis factor (TNF)-α, and plasma C reactive protein [85,88,90,91], and bacterial proliferation [88,92] being the most explored factors that contribute to the impaired healing process.”
BackgroundO’Donnell, T. F., Passman, M. A., Marston, W. A., Ennis, W. J., Dalsing, M. C., Kistner, R. L., Lurie, F., Henke, P. K., Gloviczki, M. L., Eklöf, B., et al. (2014) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2014.04.049 · Cited by 729
Self-citationLiu, W., Yu, M., Xie, D., Wang, L., Cheng, Y., Zhu, Q., Liu, F., & Yang, L. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01756-x · Cited by 519
Pranantyo, D., Yeo, C. K., Wu, Y., Fan, C., Xu, X., Yip, Y. S., Vos, M. I. G., Mahadevegowda, S. H., Lim, P. L. K., Yang, L., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-44968-y · Cited by 408
“leads to a redox imbalance and prevention of the proper wound healing occurrence 10,11 .”
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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