title: Leukocyte infiltration and activation of the NLRP3 inflammasome in white adipose tissue following thermal injury.
abstract: OBJECTIVE
  Severe thermal injury is associated with extreme and prolonged inflammatory and hypermetabolic responses, resulting in significant catabolism that delays recovery or even leads to multiple organ failure and death. Burned patients exhibit many symptoms of stress-induced diabetes, including hyperglycemia, hyperinsulinemia, and hyperlipidemia. Recently, the nucleotide-binding domain, leucine-rich family (NLR), pyrin-containing 3 (NLRP3) inflammasome has received much attention as the sensor of endogenous "danger signals" and mediator of "sterile inflammation" in type II diabetes. Therefore, we investigated whether the NLRP3 inflammasome is activated in the adipose tissue of burned patients, as we hypothesize that, similar to the scenario observed in chronic diabetes, the cytokines produced by the inflammasome mediate insulin resistance and metabolic dysfunction.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  Ross Tilley Burn Centre & Sunnybrook Research Institute.
  
  
  METHODS
  We enrolled 76 patients with burn sizes ranging from 1% to 70% total body surface area. All severely burned patients exhibited burn-induced insulin resistance and hyperglycemia.
  
  
  METHODS
  None.
  
  
  RESULTS
  We examined the adipose tissue of control and burned patients and found, via flow cytometry and gene expression studies, increased infiltration of leukocytes-especially macrophages-and evidence of inflammasome priming and activation. Furthermore, we observed increased levels of interleukin-1β in the plasma of burned patients when compared to controls.
  
  
  CONCLUSIONS
  In summary, our study is the first to show activation of the inflammasome in burned humans, and our results provide impetus for further investigation of the role of the inflammasome in burn-induced hypermetabolism and, potentially, developing novel therapies targeting this protein complex for the treatment of stress-induced diabetes.
authors.affiliation: 1Sunnybrook Research Institute, Toronto, ON, Canada. 2Department of Immunology, University of Toronto, ON, Canada. 3Division of Plastic Surgery, Department of Surgery, University of Toronto, ON, Canada. 4Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
authors.forename: Mile
authors.initials: M
authors.lastname: Stanojcic
authors.forename: Peter
authors.initials: P
authors.lastname: Chen
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Harrison
authors.forename: Vivian
authors.initials: V
authors.lastname: Wang
authors.forename: Jeremy
authors.initials: J
authors.lastname: Antonyshyn
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zúñiga-Pflücker
authors.forename: Marc G
authors.initials: MG
authors.lastname: Jeschke
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002053:Burn Units; D002056:Burns / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D006943:Hyperglycemia / Q000628:therapy; D058847:Inflammasomes / Q000378:metabolism*; D007328:Insulin / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology*; D053583:Interleukin-1beta / Q000097:blood*; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011446:Prospective Studies; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C094471:ADGRE1 protein, human; D039481:CD11b Antigen; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D058847:Inflammasomes; D007328:Insulin; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D009077:Mucins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D043562:Receptors, G-Protein-Coupled; D020170:Caspase 1