title: Serum MMP-8, -9 and TIMP-1 in sepsis: high serum levels of MMP-8 and TIMP-1 are associated with fatal outcome in a multicentre, prospective cohort study. Hypothetical impact of tetracyclines.
abstract: Recent evidence suggests that matrix metalloproteinases (MMPs) and their endogenous inhibitors are involved in the pathogenesis of sepsis. We studied serum levels of MMP-8, MMP-9 and TIMP-1 (tissue inhibitor of matrix metalloproteinase-1) in a multicentre, prospective cohort study of patients with sepsis treated in Intensive Care Units (ICUs). We analyzed serum samples taken on ICU admission from 248 critically ill sepsis patients. MMP-8, -9 and TIMP-1 serum levels were analyzed by enzyme-linked immunosorbent assays. Serum MMP-8, MMP-9 and TIMP-1 levels were significantly higher in patients with severe sepsis than in healthy controls. Serum MMP-8 levels among non-survivors (n=33) were significantly (p=0.006) higher than among survivors (n=215). Serum TIMP-1 but not MMP-9 levels were significantly higher among non-survivors than survivors (p<0.0001, p=0.079, respectively). Systemic MMP-8 is upregulated in sepsis suggesting that MMP-8 may contribute to the host response during sepsis. High serum MMP-8 and TIMP-1 levels at ICU admission were seen among patients with fatal outcome. With this background, clinical studies examining the ability of MMP-inhibitors (such as the non-antimicrobial properties of tetracyclines) to diminish the MMP-mediated inflammatory response are needed to develop novel therapies in order to improve the outcome of sepsis.
authors: Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors: Anneli
authors: A
authors: Lauhio
authors: Johanna
authors: J
authors: Hästbacka
authors: Ville
authors: V
authors: Pettilä
authors: Taina
authors: T
authors: Tervahartiala
authors: Sari
authors: S
authors: Karlsson
authors: Tero
authors: T
authors: Varpula
authors: Marjut
authors: M
authors: Varpula
authors: Esko
authors: E
authors: Ruokonen
authors: Timo
authors: T
authors: Sorsa
authors: Elina
authors: E
authors: Kolho
mesh_terms: D000328:Adult; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000401:mortality; D012772:Shock, Septic / Q000097:blood* / Q000401:mortality; D013754:Tetracyclines / Q000627:therapeutic use; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D013754:Tetracyclines; D019715:Tissue Inhibitor of Metalloproteinase-1; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9