Matrix metalloproteinases -8 and -9 and tissue inhibitor of metalloproteinase-1 in burn patients. A prospective observational study

PLoS One. 2015 May 6;10(5):e0125918. doi: 10.1371/journal.pone.0125918. eCollection 2015.

Abstract

Introduction: 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.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Blister / immunology
  • Burns / blood*
  • Burns / immunology
  • Female
  • Humans
  • Inflammation / immunology
  • Male
  • Matrix Metalloproteinase 8 / blood*
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Neutrophils / immunology*
  • Prospective Studies
  • Tissue Inhibitor of Metalloproteinase-1 / blood*

Substances

  • Biomarkers
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • MMP8 protein, human
  • Matrix Metalloproteinase 8
  • MMP9 protein, human
  • Matrix Metalloproteinase 9

Grants and funding

Finnish Society of Intensive Care (www.sthy.fi) JH, Grants (TYH 2012210, 2013353, 2014244) from Helsinki University Central Hospital Research Foundation TS, Brandforsk (www.brandforsk.se) FH, County Council of Uppsala (www.lul.se) FH, and the Swedish Society of Medicine (www.sls.se) FH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.