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

Pharmacol Res. 2011 Dec;64(6):590-4. doi: 10.1016/j.phrs.2011.06.019. Epub 2011 Jul 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Finland / epidemiology
  • Humans
  • Intensive Care Units
  • Male
  • Matrix Metalloproteinase 8 / blood*
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Prospective Studies
  • Sepsis / blood*
  • Sepsis / mortality
  • Shock, Septic / blood*
  • Shock, Septic / mortality
  • Tetracyclines / therapeutic use
  • Tissue Inhibitor of Metalloproteinase-1 / blood*


  • Tetracyclines
  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9