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Cytokines and Venous Leg Ulcer Healing-A Systematic Review
Ewa A Burian1, Lubna Sabah1, Tonny Karlsmark1
1Department of Dermato-Venereology & Wound Healing Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark.
International Journal of Molecular Sciences
|June 24, 2022
Summary
Cytokine levels, including growth factors, are linked to venous leg ulcer (VLU) healing. Non-healing VLUs show higher pro-inflammatory cytokines, suggesting immune system involvement.
Area of Science:
- Wound Healing Research
- Immunology
- Biochemistry
Background:
- Venous leg ulcers (VLUs) are common, causing significant socioeconomic burden due to delayed healing.
- Cytokines, including growth factors, are implicated in the pathogenesis of VLUs.
Purpose of the Study:
- To systematically review the association between cytokine levels and VLU healing.
- To identify specific cytokines potentially involved in VLU pathogenesis and healing outcomes.
Main Methods:
- Systematic literature search of PubMed, Embase, Web of Science, and Cochrane Library up to August 2021.
- Inclusion of 28 articles investigating 38 cytokines in 790 patients.
- Analysis of cytokine levels in wound fluid, biopsies, and serum.
Main Results:
- Weak evidence suggests elevated IL-1α, IL-6, IL-8, TNF-α, and VEGF in non-healing VLUs, with levels decreasing upon healing.
- Transforming growth factor-beta 1 (TGF-β1) levels tended to increase with VLU healing.
- Studies exhibited moderate to high risk of bias, with inconsistent and conflicting results, precluding meta-analysis.
Conclusions:
- Non-healing VLUs may be associated with elevated pro-inflammatory cytokines, indicating potential innate immune activation.
- Further research is needed on cytokines like EGF, FGF-2, GM-CSF, IL-1β, IL-1Ra, and PDGF-AA/PDGF-BB.
- A paucity of reliable longitudinal studies monitoring dynamic cytokine changes during VLU healing exists.
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