Matrix metalloproteinases and TIMP in acute respiratory distress syndrome

To investigate the implication of extracellular matrix proteinases in acute respiratory distress syndrome (ARDS), we determined 92 kD gelatinase (92 G'ase) and its natural antagonist, the tissue inhibitor of metalloproteinases-1 (TIMP) in bronchoalveolar lavage fluid (BALF) and plasma of 33 intensive care unit (ICU) patients presenting with trauma or septic shock. Eleven of these patients developed short-course ARDS, nine developed prolonged ARDS, and 13 did not progress to ARDS. Ten non-ICU patients served as controls. During the early phase of disease, 92 G'ase in BALF of ICU patients was higher than in controls, but plasma levels were not different. TIMP was increased in BALF and plasma in ARDS as compared with those of patients at risk. The 92 G'ase/TIMP ratio in BALF remained elevated in late phases of prolonged ARDS. The high intrapulmonary levels of 92 G'ase in patients at risk and with ARDS may reflect increased turnover of extracellular matrix in acute lung injury. Increased TIMP may interfere with tissue repair and fibrosis by its inhibition of 92 G'ase. Interleukin-6 (IL-6) could be involved in enhanced local synthesis of TIMP. The balance between 92 G'ase and TIMP may play an important role in lung remodeling, which is characteristic of ARDS.