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Published on: August 23, 2022
Persistent immune dysregulation consistent with chronic low-grade inflammation in paediatric burn survivors
Donna Langley1, Andrew J A Holland2, Giorgio Stefanutti3
1School of Biomedical Sciences, Faculty of Health, Queensland University of Technology (QUT), Centre for Children's Health Research, South Brisbane, Queensland, Australia; Centre for Immunology and Infection Control (CIIC), QIMR Berghofer Medical Research Institute, Queensland University of Technology (QUT), Brisbane, Queensland, Australia; Centre for Biomedical Technology (CBT), Queensland University of Technology (QUT), Kelvin Grove, Queensland, Australia.
Insights
Paediatric burn survivors with hypertrophic scars show long-term immune system changes and ongoing inflammation years after injury. These immune alterations may be linked to pathological scarring, but further research is needed.
Area of Science:
- Immunology
- Dermatology
- Paediatric Medicine
Background:
- Hypertrophic scarring is a common complication in paediatric burn survivors.
- Long-term immune dysregulation and inflammation may contribute to scar development.
- Understanding these changes is crucial for developing targeted therapies.
Purpose of the Study:
- To characterise long-term immune dysregulation in paediatric burn survivors with hypertrophic scarring.
- To investigate persistent inflammatory signalling in these patients.
- To compare immune profiles with healthy controls.
Main Methods:
- Analysis of peripheral blood mononuclear cells and plasma from 20 paediatric participants (10 burn survivors with scars, 10 controls).
- Utilisation of multiparameter flow cytometry, multiplex cytokine analysis, and qRT-PCR.
- Assessment of immune cell phenotypes, inflammatory mediators, and gene expression.
Main Results:
- Burn survivors showed increased CD4+TNFα+ cells, Th17 cells, specific natural killer T-like and natural killer cell populations, and IL-23-expressing macrophages.
- Elevated regulatory T cells (Tregs) were observed in the scar group.
- Significantly higher plasma concentrations of IL-1β, TNF-α, IL-12p70, IL-17A, and IL-23 were found, along with upregulated NFκB1 and IL-17 gene expression.
Conclusions:
- Paediatric burn survivors with hypertrophic scarring exhibit persistent systemic immune dysregulation years post-injury.
- The study highlights specific immune cell populations and inflammatory pathways involved.
- Further investigation is needed to determine if these alterations are specific to pathological scarring or general post-burn effects.
Objectives:
To characterise long-term immune dysregulation and persistent inflammatory signalling in paediatric burn survivors with hypertrophic scarring.
Methods:
Peripheral blood mononuclear cells and plasma were analysed from 20 paediatric participants: 10 burn survivors with hypertrophic scarring (median 4.1 years post-injury) and 10 age- and sex-matched healthy controls. Multiparameter flow cytometry, multiplex cytokine analysis, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to assess immune cell phenotypes, inflammatory mediators, and inflammatory gene expression.
Results:
Overall proportions of major immune cell subsets were comparable between groups. However, burn survivors with hypertrophic scarring demonstrated increased CD4⁺TNFα⁺ cells, Th17 cells, CCR6⁺ natural killer T-like cells, IL-23⁺ natural killer cells, and IL-23-expressing macrophage populations (all P < 0.05). Regulatory T cells (Tregs) and CCR4⁺CCR6⁺ double-positive Tregs were also increased (P < 0.05). Plasma concentrations of IL-1β, tumour necrosis factor-α, IL-12p70, IL-17A, and IL-23 were significantly elevated in the scar group (all P < 0.05). Gene expression analysis identified persistent upregulation of nuclear factor kappa B1 (NFκB1; 2.21-fold) and IL-17 (3.38-fold).
Conclusion:
Paediatric burn survivors with hypertrophic scarring demonstrate persistent systemic immune dysregulation several years after injury. However, the cross-sectional design and absence of a normotrophic burn control group limit conclusions regarding whether these immune alterations are specific to pathological scarring or reflect broader long-term post-burn immune dysregulation.
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