Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice
Abstract
To clarify interleukin (IL)-6 roles in wound healing, we prepared skin excisions in wild-type (WT) and IL-6-deficient BALB/c [knockout (KO)] mice. In WT mice, the wound area was reduced to 50% of original size at 6 days after injury. Microscopically, leukocyte infiltration was evident at wound sites. Furthermore, the re-epithelialization rate was ∼80% at 6 days after injury with increases in angiogenesis and hydroxyproline contents. The gene expression of IL-1, chemokines, adhesion molecules, transforming growth factor-β1, and vascular endothelial growth factor was enhanced at the wound sites. In contrast, the enhanced expression of these genes was significantly reduced in KO mice. Moreover, in KO mice, the reduction of wound area was delayed with attenuated leukocyte infiltration, re-epithelialization, angiogenesis, and collagen accumulation. Finally, the administration of a neutralizing anti-IL-6 monoclonal antibody significantly delayed wound closure in WT mice. These observations suggest that IL-6 has crucial roles in wound healing, probably by regulating leukocyte infiltration, angiogenesis, and collagen accumulation.
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Wounds without IL-6 lack an appropriate inflammatory response and demonstrate stunted angiogenesis, collagen accumulation, and re-epithelialization.
“Wounds without IL-6 lack an appropriate inflammatory response and demonstrate stunted angiogenesis, collagen accumulation, and re-epithelialization [89].”
From Immunology of Wound Healing (2018) · cites this paper as [89]
The essential involvement of IL-6 in the skin wound healing process is evidenced by delayed wound healing in IL-6−/− mice.
“The essential involvement of IL-6 in the skin wound healing process is evidenced by delayed wound healing in IL-6−/− mice.67,68”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [67]
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- Authors
- Lin, Z.-Q., Kondo, T., Ishida, Y., Takayasu, T., & Mukaida, N.
- Affiliations
- Department of Forensic & Social Environmental Medicine, Graduate School of Medical Science, Kanazawa University , Japan
- Kanazawa University (JP)
- Corresponding author
- Mukaida, Naofumi
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-06-01
- Volume
- 73
- Issue
- 6
- Pages
- 713-721
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W1987408673
- Cited by
- 585
- References
- 39
- Citations by year
- 2026: 25 · 2025: 35 · 2024: 36 · 2023: 29 · 2022: 33 · 2021: 45 · 2020: 41 · 2019: 30 · 2018: 28 · 2017: 43 · 2016: 34 · 2015: 24 · 2014: 21 · 2013: 28 · 2012: 21
- FWCI
- 13.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science, and Technology
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- interleukin-6, skin wound healing, IL-6 knockout mice, re-epithelialization, angiogenesis, collagen deposition, leukocyte infiltration, chemokines, adhesion molecules, TGF-β1, vascular endothelial growth factor, anti-IL-6 monoclonal antibody, excision wound
- MeSH terms
- Acute-Phase Proteins, Animals, Cell Movement, Epidermis, Female, Growth Substances, Hydroxyproline, Kinetics, Leukocytes, Male, Mice, Inbred BALB C, Platelet Count, Skin, Skin Physiological Phenomena, Transcription, Genetic, Wound Healing, Cell Adhesion Molecules, Interleukin-6, Cytokines, Mice, Knockout, Neovascularization, Physiologic, Chemokines, Mice
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