Tumor Necrosis Factor Alpha Inhibits Wound Healing in the Rat
Abstract
This work was undertaken to study the effects of tumor necrosis factor-α (TNF-α/cachectin) on developing granulation tissue in rats. Cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the two test groups the implants were injected daily for 4 days with a solution containing either 50 or 200 ng of TNF-α, while the implants of the control group were treated correspondingly with phosphate-buffered saline solution only. Analyses of granulation tissue and wound fluid in the sponge implants were carried out 7, 14 and 21 days after implantation. In histological specimens the ingrowth rate of granulation tissue into the sponge was significantly lower after 7 days in the group treated with 200 ng of TNF-α. No such an effect was observed after 14 or 21 days. After 7 days, the mean amounts of nucleic acids reflecting cellularity in the granulation tissue decreased dose-dependently, but nonsignificantly, in the groups treated with TNF-α. Simultaneously, the accumulation of collagen hydroxyproline of the sponge was significantly lower in the group treated with 200 ng of TNF-α than in the controls (–30%, one-way analysis of variance). This effect was not observed after 14 or 21 days. No significant differences were detected in the amounts of nitrogen, hexosamines and uronic acids between the groups, reflecting unchanged accumulation of glycosaminoglycans in the developing granulation tissue. No difference was detected in interleukin-1 activity of the wound fluid between the control and TNF-α-treated groups. These findings demonstrate that TNF-α treatment inhibits wound healing during its inflammatory phase by decreasing production of new granulation tissue. However, this effect disappears at later phases of healing.
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There are contradictory reports on the effects of locally applied TNFα on granulation tissue formation in skin wound healing, indicating there is no consensus on the effects of local TNFα application.
“There are contradictory reports on the effects of locally applied TNFα on granulation tissue formation in skin wound healing,59,64,65 indicating there is no consensus on the effects of local TNFα application.”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [59]
Elevation of TNFα leads to decreased production of granulation tissue, whereas low doses of TNFα promote collagen disposition.
“Elevation of TNFα leads to decreased production of granulation tissue, whereas low doses of TNFα promote collagen disposition,58–61 demonstrating the importance of accurate cytokine regulation during wound healing.”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [59]
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“Earlier studies have reported that TNF-α application decreased the expression of collagen and reduced the tensile strength of the wound [41,42].”
BackgroundThe Innate Immune System in Acute and Chronic Wounds
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ResultIn Vivo Effect of Tumor Necrosis Factor Alpha on Wound Angiogenesis and Epithelialization
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- Authors
- Rapala, K., Laato, M., Niinikoski, J., Kujari, H., Söder, O., Mauviel, A., & Pujol, J.-P.
- Affiliations
- University of Turku (FI)
- Venue
- European Surgical Research
- Publisher
- S. Karger AG
- Published
- 2008-04-23
- Volume
- 23
- Issue
- 5-6
- Pages
- 261-268
- ISSN
- 0014-312X (ISSN-L)
- 1421-9921
- OpenAlex
- W1978909994
- Cited by
- 71
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 7 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 3
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Surgical Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- TNF-α, wound healing, granulation tissue, collagen deposition, hydroxyproline, dose-dependent effects, nucleic acids, glycosaminoglycans, wound fluid
- MeSH terms
- Animals, Collagen, Dose-Response Relationship, Drug, Interleukin-1, Male, Rats, Inbred Strains, Tumor Necrosis Factor-alpha, Wound Healing, Rats
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