title: Matrix metalloproteinases -8 and -9 and tissue inhibitor of metalloproteinase-1 in burn patients. A prospective observational study.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients.
  
  
  METHODS
  In this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels between TBSA<20% (N = 19) and TBSA>20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids were also studied.
  
  
  RESULTS
  Plasma MMP-8 and -9 were higher in patients than in healthy controls (P<0.001 and P = 0.016), but only MMP-8 differed between the TBSA<20% and TBSA>20% groups. MMP-8 and -9 were not associated with clinical severity or outcome measures. TIMP-1 differed significantly between patients and controls (P<0.001) and between TBSA<20% and TBSA>20% groups (P<0.002). TIMP-1 was associated with 90-day mortality and correlated with the extent of injury and clinical measures of disease severity. TIMP-1 may serve as a new biomarker in outcome prognostication of burn patients.
authors.affiliation: Intensive Care Medicine, Department of Anesthesiology, Intensive Care Medicine and Pain Medicine, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Hästbacka
authors.affiliation: Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden; Burn Center, Department of Plastic- and Maxillofacial Surgery, University Hospital of Uppsala, Uppsala, Sweden.
authors.forename: Filip
authors.initials: F
authors.lastname: Fredén
authors.affiliation: Intensive Care Medicine, Department of Anesthesiology, Intensive Care Medicine and Pain Medicine, Helsinki University Hospital, Helsinki, Finland; Department of Plastic Surgery, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Maarit
authors.initials: M
authors.lastname: Hult
authors.affiliation: Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Bergquist
authors.affiliation: Intensive Care Medicine, Department of Anesthesiology, Intensive Care Medicine and Pain Medicine, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Erika
authors.initials: E
authors.lastname: Wilkman
authors.affiliation: Department of Plastic Surgery, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Jyrki
authors.initials: J
authors.lastname: Vuola
authors.affiliation: Department of Oral and Maxillofacial Surgery, Helsinki University Hospital, Helsinki, Finland; Division of Periodontology, Department of Dental Medicine, Karolinska Institute, Huddinge, Sweden.
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.affiliation: Department of Oral and Maxillofacial Surgery, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Tervahartiala
authors.affiliation: Department of Surgical Sciences, Plastic Surgery, Uppsala University, Uppsala, Sweden; Burn Center, Department of Plastic- and Maxillofacial Surgery, University Hospital of Uppsala, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Huss
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001768:Blister / Q000276:immunology; D002056:Burns / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D011446:Prospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9