Systemic administration of interferon-gamma impairs wound healing
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Updated: Nov 9, 2026
Experimental Infection with Listeria monocytogenes as a Model for Studying Host Interferon-γ Responses
Published on: November 16, 2016
R H Miles1, T P Paxton, D Zacheis
1Department of Surgery, Loyola University, Maywood, Illinois 20153.
Abstract:
Interferon-gamma (IFN-gamma), a cytokine that has been shown to upregulate macrophage function, has recently been demonstrated to improve outcome when exogenously administered in several animal models of injury. Because the macrophage is also important in the events that govern wound healing, we evaluated the effects of IFN-gamma upon wound healing in a murine model. IFN-gamma was administered in doses of 937.5-22,500 u synchronous with the creation of a left paraspinous wound and then daily. At Day 10, wounds were harvested, evaluated for wound disruption strength (WDS), and subjected to morphometric analysis. Wounds were also subjected to 36-hr formalin fixation to maximally cross-link collagen fibrils and retested for WDS. We found that IFN-gamma impaired wound healing at all doses relative to control, and WDS was impaired in a dose-dependent fashion. Our highest dose of IFN-gamma (22,500 u) produced a WDS only 65% of the control. Morphometric studies demonstrated less collagen deposition and a lower degree of neovascularity in IFN-gamma-treated animals. In addition, formalin fixation studies suggested that IFN-gamma may impair collagen cross-linking. The potential benefits of IFN-gamma in the multiply injured patient must be weighed against the possibility that IFN-gamma might deleteriously effect events fundamental to wound healing.
Insights
Interferon-gamma (IFN-gamma) administration impaired wound healing in mice. This cytokine negatively affected wound disruption strength, collagen deposition, and neovascularity, suggesting potential detrimental effects on healing processes.
Area of Science:
- Immunology
- Wound Healing Research
- Biomedical Science
Background:
- Interferon-gamma (IFN-gamma) is a cytokine known to enhance macrophage function.
- Exogenous administration of IFN-gamma has shown positive outcomes in various animal injury models.
- Macrophages play a crucial role in the complex processes of wound healing.
Purpose of the Study:
- To investigate the specific effects of exogenous Interferon-gamma (IFN-gamma) on wound healing.
- To determine if IFN-gamma influences key aspects of the wound healing cascade in a murine model.
Main Methods:
- A murine model with paraspinous wounds was utilized.
- Interferon-gamma (IFN-gamma) was administered daily at varying doses (937.5–22,500 U) starting at wound creation.
- Wound healing was assessed on Day 10 by measuring wound disruption strength (WDS), performing morphometric analysis, and evaluating collagen cross-linking after formalin fixation.
Main Results:
- Interferon-gamma (IFN-gamma) administration resulted in impaired wound healing across all tested doses.
- A dose-dependent decrease in wound disruption strength (WDS) was observed, with the highest dose yielding only 65% of control WDS.
- Morphometric analysis revealed reduced collagen deposition and neovascularization in IFN-gamma treated wounds.
- Formalin fixation studies indicated that IFN-gamma may also hinder collagen cross-linking.
Conclusions:
- Exogenous administration of Interferon-gamma (IFN-gamma) appears to be detrimental to wound healing in this murine model.
- The observed impairment in WDS, collagen deposition, and neovascularity suggests a negative impact on critical healing mechanisms.
- Clinicians should consider the potential adverse effects of IFN-gamma on wound healing when treating multiply injured patients.
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