Interleukin-1α and Collagenase Activity Are Elevated in Chronic Wounds
Abstract
Interleukin-1-alpha (IL-1α) is a member of a family of proinflammatory polypeptide mediators that has been shown in vitro to stimulate collagenase production. Collagenase is a proteolytic enzyme classified as one of the matrix metalloproteinases (MMP-1) that specifically recognizes and cleaves collagen. Therefore, the objective of this study was to compare the levels of these two proteins in chronic wounds as possible factors in the pathogenesis of chronic wounds. Fluids from 10 chronic wounds were collected before and after a 1-week treatment with a hydroactive dressing (Cutinova cavity). In addition, fluids were collected from 20 acute wounds for comparison. IL-lα and MMP-1 levels were quantified using sandwich ELISA. Collagenase activity was measured using a radiolabeled collagen as substrate. Clinically, the chronic wounds showed decreased area (-21.0 cm2) and reduced volume (-134.5 cm3) by 4 weeks after treatment with the hydroactive dressing. There were no significant differences in the protein concentrations between acute wound fluids (21.0 ± 3.0 mg/ml) and chronic wound fluids before and after treatment with the hydroactive dressing (18.3 ± 5.5 and 25.2 ± 7.6 mg/ml, respectively). Levels of IL-1α in the acute wound fluids were low (0.019 pg/mg), whereas in the chronic wound fluid before treatment they had been significantly elevated (44.9 + 21.8 pg/mg). Following treatment with the hydroactive dressing, the IL-1α levels dropped to 10.3 + 3.3 pg/mg (p < 0.05). Collagenase activity was not detectable in acute wound fluid, elevated in pretreatment chronic wounds (12.9 + 3.4 units), and decreased in chronic wounds after treatment (11.4 + 3.3 units). This study correlated clinical healing of chronic wounds with biochemical changes in the ulcer microenvironment. As the chronic wounds began to heal, there was a significant decrease in the IL-1α levels and collagenase activity, thus suggesting that these two proteins may contribute to the lack of healing characteristic of chronic wounds. (Plast. Reconstr. Surg. 102: 1023, 1998.)
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
As IL-1α has been shown to stimulate collagenase production, IL-1α overproduction may be mechanistically linked to impaired wound healing through cleavage of collagen.
“As IL-1α has been shown to stimulate collagenase production, IL-1α overproduction may be mechanistically linked to impaired wound healing through cleavage of collagen.53”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [53]
Cited by
Sorted by citations
The Role of Vascular Endothelial Growth Factor in Wound Healing
Bao, P. Q., Kodra, A., Tomic‐Canic, M., Golinko, M. S., Ehrlich, H. P., & Brem, H. (2008) · Journal of Surgical Research · doi:10.1016/j.jss.2008.04.023 · Cited by 1,216 · see citing works
The Immune Functions of Keratinocytes in Skin Wound Healing
Piipponen, M., Li, D., & Xu, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228790 · Cited by 521 · see citing works
Proteases and Delayed Wound Healing
McCarty, S. M., & Percival, S. L. (2013) · Advances in Wound Care · doi:10.1089/wound.2012.0370 · Cited by 478 · see citing works
The proteolytic environment of chronic wounds
Yager, D. R., & Nwomeh, B. C. (1999) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.1999.00433.x · Cited by 399 · see citing works
Self-citationLADWIG, G. P., Robson, M. C., Liu, R., Kuhn, M. A., Muir, D., & Schultz, G. S. (2002) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2002.10903.x · Cited by 355 · see citing works
The Innate Immune System in Acute and Chronic Wounds
MacLeod, A. S., & Mansbridge, J. N. (2016) · Advances in Wound Care · doi:10.1089/wound.2014.0608 · Cited by 289 · see citing works
“As IL-1a has been shown to stimulate collagenase production, IL-1a overproduction may be mechanistically linked to impaired wound healing through cleavage of collagen.(53) Furthermore, skin injury, induced either by UV radiation, skin irritants, or trauma, has been shown to liberate ATP into the extracellular space, w…”
BackgroundKruse, C., Singh, M., Targosinski, S., Sinha, I., Sørensen, J. A., Eriksson, E. K., & Nuutila, K. (2017) · Wound Repair and Regeneration · doi:10.1111/wrr.12526 · Cited by 252 · see citing works
“A persisting high level of IL-1a has previously been found in chronic wounds, suggesting that a continuous high expression of IL-1 a prevents the wound from healing.(31) Based on our literature review, this is the first study that has investigated the role of pH on wound healing in a controlled fashion both in vitro a…”
BackgroundBeidler, S. K., Douillet, C. D., Berndt, D. F., Keagy, B. A., Rich, P. B., & Marston, W. A. (2009) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2008.11.049 · Cited by 223 · see citing works
“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…”
ResultLazaro, J. L., Izzo, V., Meaume, S., Davies, A. H., Lobmann, R., & Uccioli, L. (2016) · Journal of Wound Care · doi:10.12968/jowc.2016.25.5.277 · Cited by 185 · see citing works
Matrix metalloproteinases: The sculptors of chronic cutaneous wounds
Krishnaswamy, V. R., Mintz, D., & Sagi, I. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2017.08.003 · Cited by 184 · see citing works
Excessive neutrophils characterize chronic pressure ulcers
Diegelmann, R. F. (2003) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2003.11617.x · Cited by 168 · see citing works
“Other studies have found that nonhealing ulcers contain elevated amounts of interleukin-1a (IL-1a) and collagenolytic activity.(11) There was a correlated decrease in both IL-1a and collagenolytic activity when these wounds were successfully treated with a hydroactive dressing (Cutinova Cavity) and began to heal.”
BackgroundSelf-citationCytokines and Wound Healing: The Role of Cytokine and Anticytokine Therapy in the Repair Response
Efron, P. A., & Moldawer, L. L. (2004) · Journal of Burn Care & Rehabilitation · doi:10.1097/01.bcr.0000111766.97335.34 · Cited by 141 · see citing works
Age-Related Changes in Wound Healing
Thomas, D. R. (2001) · Drugs & Aging · doi:10.2165/00002512-200118080-00005 · Cited by 133 · see citing works
Wiegand, C., Schönfelder, U., Abel, M., et al. (2009) · Archives of Dermatological Research · doi:10.1007/s00403-009-1011-1 · Cited by 113 · see citing works
The Role of Doxycycline as a Matrix Metalloproteinase Inhibitor for the Treatment of Chronic Wounds
Stechmiller, J. K., Cowan, L. J., & Schultz, G. S. (2009) · Biological Research For Nursing · doi:10.1177/1099800409346333 · Cited by 112 · see citing works
“Previous studies (Barone et al., 1998; Mackelfresh, Soon, & Arbiser, 2005; Nwomeh, Liang, Cohen, & Yager, 1999; Nwomeh, Liang, Diegelmann, Cohen, & Yager, 1998; Wysocki & Grinnell, 1990; Wysocki et al., 1993; Yager & Nwomeh, 1999; Yager et al., 1996), confirmed by Schultz et al. (1992) and…”
Quantification of Cytokines Involved in Wound Healing Using Surface Plasmon Resonance
Battaglia, T. M., Masson, J., Sierks, M. R., et al. (2005) · Analytical Chemistry · doi:10.1021/ac050568w · Cited by 112 · see citing works
Proteinases, their inhibitors, and cytokine profiles in acute wound fluid
Baker, E. A., & Leaper, D. J. (2000) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2000.00392.x · Cited by 116 · see citing works
Wound Fluids: A Window Into the Wound Environment?
Yager, D. R., Kulina, R. A., & Gilman, L. A. (2007) · The International Journal of Lower Extremity Wounds · doi:10.1177/1534734607307035 · Cited by 103 · see citing works
“In contrast, another study observed higher levels of IL-1α, IL-1β, and IL-6 in chronic wounds.(4,22) Importantly, this same study found that levels of IL-1, IL-6, and TNF-α decreased when nonhealing wounds switched to a healing phenotype.”
BackgroundResultSelf-citationChen, C., Schultz, G. S., Bloch, M. B., et al. (1999) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.1999.00486.x · Cited by 101 · see citing works
Kumar, S., Majhi, R. K., Singh, A., Mishra, M., Tiwari, A. K., Chawla, S., Guha, P., Satpati, B., Mohapatra, H., Goswami, L., et al. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b17086 · Cited by 81 · see citing works
Inflammation 2: its role in the healing of chronic wounds
Hart, J. (2002) · Journal of Wound Care · doi:10.12968/jowc.2002.11.7.26416 · Cited by 82 · see citing works
Stojadinovic, O., Minkiewicz, J., Sawaya, A., Bourne, J. W., Torzilli, P., de Rivero Vaccari, J. P., Dietrich, W. D., Keane, R. W., & Tomic-Canic, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069223 · Cited by 77 · see citing works
“On the other hand, one should keep in mind that reports from studies showed elevated levels of IL1, TNF, MMP’s and defensins in human PU [8–15], which appears to be in contrast to the findings described here of decreased IL-1 b production in aged skin after loading.”
BackgroundWhat is the Future of Diabetic Wound Care?
Sweitzer, S. M., Fann, S. A., Borg, T. K., Baynes, J., & Yost, M. J. (2006) · The Science of Diabetes Self-Management and Care · doi:10.1177/0145721706286897 · Cited by 60 · see citing works
Licinio, J., & Frost, P. (2000) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2000001000003 · Cited by 58 · see citing works
Menon, S. N., Flegg, J. A., McCue, S. W., Schugart, R. C., Dawson, R., & McElwain, D. L. S. (2012) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2012.0319 · Cited by 55 · see citing works
Liu, Y. C., Margolis, D. J., & Isseroff, R. R. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2010.428 · Cited by 51 · see citing works
“The process itself usually involves aspiration of sample fluid that accumulates underneath transparent adhesive dressing (Barone et al., 1998; Nwomeh et al., 1999).”
BackgroundMannello, F., Ligi, D., Canale, M., & Raffetto, J. D. (2014) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.2014.927312 · Cited by 52 · see citing works
“Levels of the active forms of both uPA and its inhibitor plasminogen activator inhibitor (PAI) were found elevated in CVUWF, but were downregulated as healing progressed, mainly due to uPA/PAI-1 complex formation [158,160,176].”
BackgroundTuli, S. S., Liu, R., Chen, C., et al. (2006) · Current Eye Research · doi:10.1080/02713680600837390 · Cited by 50 · see citing works
Evidence-Based Medicine: Wound Management
Jones, C. M., Rothermel, A. T., & Mackay, D. R. (2017) · Plastic & Reconstructive Surgery · doi:10.1097/prs.0000000000003486 · Cited by 64 · see citing works
Vita, G. D., Patti, R., D’Agostino, P., et al. (2006) · Wound Repair and Regeneration · doi:10.1111/j.1743-6109.2006.00120.x · Cited by 46 · see citing works
“Indeed, persistently high levels of IL-1a after the first week are deleterious and pathogenic.(26,27) The secretion of IL-1ra parallels the secretion of IL-1a, functioning as a competitive inhibitor of IL-1 receptor binding in vitro and in vivo, and antagonizing the activities of both molecular forms of IL-1 without h…”
BackgroundWound Fluid in Diabetic Foot Ulceration
Loeffler, M. W., Schuster, H., Bühler, S., & Beckert, S. (2013) · The International Journal of Lower Extremity Wounds · doi:10.1177/1534734613489989 · Cited by 45 · see citing works
“IL-1α as a prototype pro-inflammatory mediator has been seen in very high amounts.(125) The basic motif of chronic inflammatory activity is further underlined by elevated levels of IL-6,(91,100) IL-8,(100) and TNFα.”
BackgroundWhat Can Wound Fluids Tell Us About the Venous Ulcer Microenvironment?
Drinkwater, S. L., Smith, A., & Burnand, K. G. (2002) · The International Journal of Lower Extremity Wounds · doi:10.1177/153473460200100307 · Cited by 43 · see citing works
Proteomics in chronic wound research: Potentials in healing and health
Broadbent, J. A., Walsh, T., & Upton, Z. (2010) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.200900152 · Cited by 44 · see citing works
Schmohl, M., Beckert, S., Joos, T. O., Königsrainer, A., Schneiderhan‐Marra, N., & Loeffler, M. W. (2012) · Diabetes Care · doi:10.2337/dc11-2547 · Cited by 40 · see citing works
“Comparison of levels of cytokines, chemokines, andMMPs demonstrated no relevant loss of analytes when using the swabbing technique compared with the currently available standard method.”
MethodInfluentialShi, L., Ramsay, S., Ermis, R., & Carson, D. L. (2011) · International Wound Journal · doi:10.1111/j.1742-481x.2011.00843.x · Cited by 39 · see citing works
Dynamics of Wound Healing after Silicone Device Implantation
Shanklin, D. R., & Smalley, D. L. (1999) · Experimental and Molecular Pathology · doi:10.1006/exmp.1999.2269 · Cited by 36 · see citing works
Autologous fibroblasts to treat deep and complicated leg ulcers in diabetic patients
Cavallini, M. (2007) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2006.00182.x · Cited by 35 · see citing works
Kanji, S., Das, M., Aggarwal, R., Lu, J., Joseph, M., Basu, S., Pompili, V. J., & Das, H. (2013) · Stem Cell Research · doi:10.1016/j.scr.2013.11.005 · Cited by 34 · see citing works
“Inflammation is crucial to the normal wound healing process, however, persistent inflammation leads to impaired healing (Barone et al., 1998; Stadelmann et al., 1998; Trengove et al., 2000; Zhou et al., 2000).”
BackgroundAlaseirlis, D. A., Li, Y., Çilli, F., et al. (2005) · Connective Tissue Research · doi:10.1080/03008200590935501 · Cited by 29 · see citing works
“Further, persistent inflammation has long been associated with chronic nonhealing skin wounds [1, 24].”
BackgroundPerumal, J., Lim, H. Q., Attia, A. B. E., Raziq, R., Leavesley, D. I., Upton, Z., Dinish, U. S., & Olivo, M. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s303130 · Cited by 27 · see citing works
Vita, G. D., Patti, R., D’Agostino, P., et al. (2006) · The American Journal of Surgery · doi:10.1016/j.amjsurg.2005.11.008 · Cited by 26 · see citing works
Chemokines as Therapeutic Targets to Improve Healing Efficiency of Chronic Wounds
Satish, L. (2014) · Advances in Wound Care · doi:10.1089/wound.2014.0602 · Cited by 26 · see citing works
Akt inhibition up‐regulates MMP1 through a CCN2‐dependent pathway in human dermal fibroblasts
Bujor, A. M., Nakerakanti, S., Morris, E., et al. (2010) · Experimental Dermatology · doi:10.1111/j.1600-0625.2010.01065.x · Cited by 19 · see citing works
Lu, Y.-E., & Chen, Y. (2021) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2021.109395 · Cited by 18 · see citing works
Wound fluid sampling methods for proteomic studies: A scoping review
Harvey, J., Mellody, K. T., Cullum, N. A., Watson, R. E. B., & Dumville, J. C. (2022) · Wound Repair and Regeneration · doi:10.1111/wrr.13009 · Cited by 17 · see citing works
“Total 100 (65) 100 (8) 100 (34) 100 (86) 100 (12) 100 (124) 100 (4) 100 (6) 100 (280) ‘All studies’ refers to the number of wound groups studied regardless of collection method used.”
Molecular finds of pressure ulcer: A bioinformatics approach in pressure ulcer
Santos, E. M., Farias, L. C., Santos, S. H. S., de Paula, A. M. B., Silva, C. S. D. O. E., & Guimarães, A. L. S. (2017) · Journal of Tissue Viability · doi:10.1016/j.jtv.2017.01.002 · Cited by 15 · see citing works
Caley, M. P., Wall, I. B., Peake, M. A., Kipling, D., Giles, P. J., Thomas, D. W., & Stephens, P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041001 · Cited by 15 · see citing works
Differentiating MMPs, Biofilm, Endotoxins, Exotoxins, and Cytokines
Fleck, C. A. (2006) · Advances in Skin & Wound Care · doi:10.1097/00129334-200603000-00008 · Cited by 12 · see citing works
“shown to be elevated in chronic wounds.(16) Trengove et al(17)”
BackgroundDevelopment of a chronic type skin defect model and a study of cytokine secretion using the model
Zhou, L., Matsui, R., & Ono, I. (2000) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2000.00304.x · Cited by 11 · see citing works
Biological wound matrices with native dermis-like collagen efficiently modulate protease activity
Tati, R., Nordin, S. L., Abdillahi, S. M., & Mörgelin, M. (2018) · Journal of Wound Care · doi:10.12968/jowc.2018.27.4.199 · Cited by 10 · see citing works
Kaur, K., Singh, A., Attri, S., Malhotra, D., Verma, A., Bedi, N., & Bedi, P. M. S. (2020) · IntechOpen eBooks · doi:10.5772/intechopen.92982 · Cited by 11 · see citing works
Perceived Stress and Surgical Wound Cytokine Patterns
Lucas, V. S., McCain, N. L., Elswick, R. K., & Pozez, A. L. (2018) · Plastic and Aesthetic Nursing · doi:10.1097/psn.0000000000000223 · Cited by 9 · see citing works
“However, elevated levels of IL-1 beyond the first 7 days of wound healing have been associated with poor wound healing outcomes (Barone et al., 1998; Trengove, Bielefeldt-Ohmann, & Stacey, 2000).”
BackgroundSelf-citationDysfunctional wound healing in chronic wounds
Stephens, P. (2011) · Elsevier eBooks · doi:10.1533/9780857093301.1.3 · Cited by 7 · see citing works
Jackson, C. J., Reppe, S., Eidet, J. R., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-08586-7 · Cited by 7 · see citing works
A New Era of Discovery in Facial Plastic Surgery
Hom, D. B. (2000) · Archives of Facial Plastic Surgery · doi:10.1001/archfaci.2.3.166 · Cited by 7 · see citing works
Inflammation in Wound Repair: Role and Function of Inflammation in Wound Repair
MacLeod, A. S., & Kwock, J. T. (2017) · Wiley eBooks · doi:10.1002/9781119282518.ch14 · Cited by 7 · see citing works
The Relationship of Nutrition and Pressure Ulcers
Thomas, D. R. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1929-1_14 · Cited by 3 · see citing works
Traditional and Nontraditional Evaluation of Wound Healing Process
Angspatt, A., Puttilerpong, C., Sirithanakorn, C., & Aramwit, P. (2018) · Recent clinical techniques, results, and research in wounds · doi:10.1007/15695_2017_106 · Cited by 2 · see citing works
The Relationship of Nutrition and Pressure Ulcers
Thomas, D. R. (2004) · Humana Press eBooks · doi:10.1007/978-1-59259-391-0_12 · Cited by 2 · see citing works
“Levels of IL-1� are elevated in pressure ulcers but low in acute wound fluid ( 63 ).”
BackgroundMin, C. H., Kim, S.-N., Kim, M. J., Lee, D., Ji, H. B., Kim, C. R., Han, J. H., Choi, J., Kim, J., & Choy, Y. B. (2026) · Biomaterials Advances · doi:10.1016/j.bioadv.2026.214876 · Cited by 3 · see citing works
The Role of Nutrition in the Management and Prevention of Pressure Ulcers
Thomas, D. R. (2013) · Humana Press eBooks · doi:10.1007/978-1-62703-700-6_8 · Cited by 1 · see citing works
Wound Healing: Physiology, Clinical Progress, Growth Factors, and the Secret of the Fetus
Efron, D. T., Witte, M. B., & Barbul, A. (2000) · Springer eBooks · doi:10.1007/978-1-4612-1222-5_56 · Cited by 1 · see citing works
- Authors
- Barone, E. J., Yager, D. R., Pozez, A. L., Olutoye, O. O., Crossland, M. C., Diegelmann, R. F., & Cohen, K. I.
- Affiliations
- Virginia Commonwealth University (US)
- Venue
- Plastic and Reconstructive Surgery
- Published
- 1998-09
- Volume
- 102
- Issue
- 4
- Pages
- 1023-1027
- ISSN
- 0032-1052 (ISSN-L)
- OpenAlex
- W4249000450
- Cited by
- 62
- References
- 0
- Citations by year
- 2026: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 6 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 5 · 2012: 2
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Plastic & Reconstructive Surgery (publishedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Keywords
- interleukin-1 alpha, collagenase activity, chronic wounds, MMP-1, wound healing, wound fluid, acute wounds
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
