Imbalance between matrix metalloproteinases (MMP-9 and MMP-2) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in acute respiratory distress syndrome patients

Crit Care Med. 2003 Feb;31(2):536-42. doi: 10.1097/01.CCM.0000048626.02184.F8.


Objective: Matrix metalloproteinases (MMPs) are known to be involved in degradation of extracellular matrix. We aimed to assess the role of MMPs and their natural inhibitors (TIMPs) in the genesis and the evolution of acute respiratory distress syndrome (ARDS).

Design: Prospective, clinical study.

Setting: Intensive care unit of a university hospital.

Patients: Twenty-one patients were assigned to three different groups: Group 1 patients developed ARDS that rapidly resolved in <4 days; Group 2 patients developed ARDS lasting >8 days; Group 3 (control group) patients had clinical criteria for hospital-acquired pneumonia without ARDS.

Intervention: Bronchoalveolar lavages were performed on day 0 of the onset of ARDS and on days 4, 8, and 12 for unresolving ARDS. For group 3, the bronchoalveolar lavages were performed on day 0 of the pneumonia. On these bronchoalveolar lavage fluids, we measured the amount of MMP-9 and -2 and their inhibitors TIMP-1 and -2.

Measurements and main results: The amount of MMP-9 measured by enzyme-linked immunosorbent assay was significantly lower in the bronchoalveolar lavages from patients with ARDS (group 1 and group 2) compared with the control group (p <.01) throughout the study. The ratio MMP-9/TIMP-1 was also significantly smaller and was less than one in the two ARDS groups (p <.05) compared with the control group (group 3), where this ratio was greater than one. In the second bronchoalveolar lavages, this ratio was greater than one only in the ARDS group that rapidly resolved (group 1), whereas it stayed less than one when the ARDS was lasting (group 2). Concerning the quantity of MMP-2 and the ratio MMP-2/TIMP-2, there was no statistical difference between the three groups throughout the study. Using zymography, there was no significant difference in the amounts of active and latent MMP-9 between the three groups. Moreover, no significant difference in the quantity of latent and active MMP-2 in the three groups was noted.

Conclusion: These results suggest that the MMP-9 level and MMP-9/TIMP-1 ratio play a role in the pathogenesis of ARDS and, namely, the imbalance between MMP-9 and TIMP-1 would participate in airway remodeling leading to either short- or long-course ARDS. The ratio MMP-9/TIMP-1 could be a predictive factor of the ARDS evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Prospective Studies
  • Respiratory Distress Syndrome / enzymology*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism*


  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9