title: Timing of excision after a non-severe burn has a significant impact on the subsequent immune response in a murine model.
abstract: BACKGROUND
  Burn excision has emerged as the dominant clinical paradigm in treatment of deep burns. Surgical intervention is common but the timing of wound excision is a balance between wound depth assessment, avoidance of infection and unnecessary intervention. However the physiological impact of timing of excision and consequences for the immune response are not well understood.
  
  
  METHODS
  Mice were subject to full-thickness burn (<8% TBSA) followed by early (day 1) or late (day 8) surgical excision. Draining lymph nodes, wound tissue and sera were collected longitudinally at day 2 and day 6 after excision and analyzed for cytokine, dendritic cell and T cell profiles using FACS and multiplex ELISA assays.
  
  
  RESULTS
  Delayed excision after injury initiated acute and severe inflammatory responses, with high levels of inflammatory cytokines, increased chemokine responses, and elevated Th2 promoting cytokines compared to early excision. Cellular inflammation in the wound was exacerbated with elevated neutrophils, eosinophil and monocytes. Wound cellular innate immune response decreased after late excision with a loss of inflammatory dendritic cells (DC), decreased NKT cells, and inhibition of NK cell activation. Systemically late excision increased trafficking conventional CD8α(-) DC to the lymph node, but there was no apparent DC activation. This was reflected in the induction of CD4T regulatory (Treg) cells and suppression of CD8T cell proliferation after late excision. No suppression was observed with early excision.
  
  
  CONCLUSIONS
  This data suggests early excision of the wound, during the phase of immune down-regulation initiated by the burn, maintains an innate and adaptive immune cell response. In contrast, late wound excision induced a severe inflammatory response, with subsequent down-regulation of innate and adaptive immune cell responses. Therefore timing of excision is critical in affecting the immune response to burn.
authors.affiliation: Burn Injury Research Unit, School of Surgery, University of Western Australia, Perth, Western Australia, Australia; Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia. Electronic address: vanessa.fear@uwa.edu.au.
authors.forename: Vanessa S
authors.initials: VS
authors.lastname: Fear
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia. Electronic address: matthew.poh@uwa.edu.au.
authors.forename: Wee-Peng
authors.initials: WP
authors.lastname: Poh
authors.affiliation: Burn Injury Research Unit, School of Surgery, University of Western Australia, Perth, Western Australia, Australia. Electronic address: Samantha.valvis@health.wa.gov.au.
authors.forename: Samantha
authors.initials: S
authors.lastname: Valvis
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia. Electronic address: Jason.Waithman@telethonkids.org.au.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Waithman
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia. Electronic address: Bree.foley@telethonkids.org.au.
authors.forename: Bree
authors.initials: B
authors.lastname: Foley
authors.affiliation: Burn Injury Research Unit, School of Surgery, University of Western Australia, Perth, Western Australia, Australia; Fiona Wood Foundation, Perth, Western Australia, Australia; Burns Service of Western Australia, WA Dept. of Health, Perth, Western Australia, Australia. Electronic address: Fiona.Wood@health.wa.gov.au.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Wood
authors.affiliation: Burn Injury Research Unit, School of Surgery, University of Western Australia, Perth, Western Australia, Australia; Burns Service of Western Australia, WA Dept. of Health, Perth, Western Australia, Australia. Electronic address: mark.fear@uwa.edu.au.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Fear
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002056:Burns / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D049109:Cell Proliferation / Q000502:physiology; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology; D005260:Female; D007113:Immunity, Innate / Q000502:physiology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D009504:Neutrophils / Q000166:cytology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D018925:Chemokines; D016207:Cytokines
keywords: Burn; Excision; Immune response; Timing