Oral Presentation ANZBA Annual Scientific Meeting 2024

Delayed Inflammatory Resolution and TGFb expressing Tregs attributed to healing outcomes in paediatric burns (#1a)

Donna Langley 1 2 3 , Andrew JA Holland 4 , Giorgio Stefanutti 5 , Roy Kimble 5 , Tony Kenna 1 2 , Leila Cuttle 1 3
  1. Burns Unit Research, Children's Health Research Centre, Queensland University of Technology (QUT), South Brisbane, QLD, Australia
  2. Centre for Immunology and Infection Control (CIIC) , QIMR Berghofer Medical Research Institute, Queensland University of Technology (QUT), Brisbane, Queensland, Australia
  3. Centre for Biomedical Technology (CBT), Queensland University of Technology (QUT), Kelvin Grove, Queensland, Australia
  4. The Children’s Hospital at Westmead Burns Unit, Kids Research Institute, Department of Paediatrics and Child Health, Sydney Medical School, The University of Sydney., Sydney, New South Wales, Australia
  5. Department of Paediatric Surgery, Urology, Burns and Trauma , Children’s Health Queensland, Queensland Children’s Hospital, South Brisbane, Queensland, Australia

Delayed healing after a burn injury is associated with poor patient outcomes. The delay may be caused by an immune dysregulation that occurs during the transition from the inflammatory to the proliferative phase of wound healing. The aim of this study was to identify inflammatory cells and mediators that may cause delayed healing in paediatric burn patients. Flow cytometry was used to measure 26 pro-inflammatory and anti-inflammatory cell markers, chemokines, and cytokines. Peripheral blood mononuclear cells from 30 paediatric patients were analysed, including 10 paediatric burn patients who had healed in less than 21 days, 10 burn patients who took longer than 21 days to heal, and 10 healthy age- and sex-matched control patients.

The overall proportions of primary lymphocytes and monocytes were unchanged between the patient and control groups. The cell profile for delayed healing appeared to be linked to an increase in proinflammatory recruitment (chemokine CCR6) and alterations in the expression of "anti-inflammatory" cytokines (IL-23 and TGFβ) on various cell subsets. There was also an increase in systemic pro-inflammatory cytokines in plasma (IL-33, IL-23, TNFα, MIP). Patients who healed faster had increased proportions of Tregs expressing TGFβ. These results suggest there is a delayed resolution of inflammation, where the inflammation should have resolved or should begin resolving - but hasn't. The unresolved inflammation increases systemic and persistent crosstalk between inflammatory cells and mediators. These factors may be a contributing factor to future co-morbidities for paediatric burn patients and are potential targets for therapeutics to improve wound healing.