title: Association of Matrix Metalloproteinases -7, -8 and -9 and TIMP -1 with Disease Severity in Acute Pancreatitis. A Cohort Study.
abstract: OBJECTIVE
  Several biomarkers for early detection of severe acute pancreatitis (SAP) have been presented. Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are released early in inflammation. We aimed to assess levels of MMP-7, -8, -9 and TIMP-1 in acute pancreatitis (AP) and explore their ability to detect disease severity. Our second aim was to find an association between MMPs, TIMP and creatinine.
  
  
  METHODS
  We collected plasma samples for MMP-7, -8, -9 and TIMP-1 analyses from 176 patients presenting within 96 h from onset of acute pancreatitis (AP) symptoms. We used samples from 32 control subjects as comparison. The revised Atlanta Classification was utilised to assess severity of disease. Receiver operating characteristic curve analysis and Spearman´s Rho-test were utilised for statistical calculations.
  
  
  RESULTS
  Compared with controls, patients showed higher levels of all studied markers. MMP-8 was higher in moderately severe AP than in mild AP (p = 0.005) and MMP-8, -9 and TIMP-1 were higher in severe than in mild AP (p<0.001, p = 0.005 and p = 0.019). MMP-8 detected SAP with an AUC of 0.939 [95% CI 0.894-0.984], LR+ 9.03 [5.30-15.39]. MMP-8, -9 and TIMP-1 failed to discern moderately severe AP from SAP. MMP-7 was not different between patient groups. MMP-7 and TIMP-1 correlated weakly with creatinine (Rho = 0.221 and 0.243). MMP-8 might be a useful biomarker in early detection of SAP.
authors: Department of Perioperative, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Eija
authors: E
authors: Nukarinen
authors: Department of GI Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Outi
authors: O
authors: Lindström
authors: Department of Bacteriology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Krista
authors: K
authors: Kuuliala
authors: Department of GI Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Leena
authors: L
authors: Kylänpää
authors: Department of Perioperative, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Ville
authors: V
authors: Pettilä
authors: Department of GI Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Pauli
authors: P
authors: Puolakkainen
authors: Department of Bacteriology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Antti
authors: A
authors: Kuuliala
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors: Mari
authors: M
authors: Hämäläinen
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors: Eeva
authors: E
authors: Moilanen
authors: Department of Bacteriology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Heikki
authors: H
authors: Repo
authors: Department of Perioperative, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Johanna
authors: J
authors: Hästbacka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood*; D020784:Matrix Metalloproteinase 8 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D015233:Models, Statistical; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood*; D012372:ROC Curve; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9