TIMP-1, TIMP-2 and MMP-9 as prognostic markers for clinical outcome in sepsis

Background

Acute inflammatory diseases such as sepsis are characterized by activation of leukocytes, which contain MMP-9 (Gelatinase B) in tertiary granules. Matrix metalloproteinases play an important role in the degradation of extracellular matrix and basement membranes by destroying the elastic lamina. These main enzymes of tissue turnover are controlled by their inhibitors such as TIMP-1 (tissue inhibitor 1 of metalloproteinase). To assess the importance of clinical outcome of septic patients we measured TIMP-1, TIMP-2, MMP-2, MMP-3 and MMP-9 in septic patients.

Patients and methods

Serum was collected from 37 septic patients admitted to the ICU with APACHE score 14.5 on day 1 (SD 7.6). Blood was collected from the 37 septic patients and from 14 healthy controls on day 1. Twelve of the 37 critically ill patients died within 28 days. We measured MMP-9, MMP-2, MMP-3, TIMP-2 and TIMP-1 serum levels from all healthy controls, from the 25 survivors and the 12 nonsurvivors with ELISA methods. We compared the serum levels of MMP-9, TIMP-2 and TIMP-1 between the three groups.

Results

MMP-9 and TIMP-1 levels (MMP-9 mean ± SD = 80 ± 86, TIMP-1 = 3216 ± 1222) in the severely ill patients were significantly higher (P < 0.001) than in controls (MMP-9 = 6 ± 7, TIMP-1 = 953 ± 184). MMP-2 showed no difference between septic patients (948 ± 287) and control group (928 ± 165). We noted a significantly (P = 0.003) increased concentration of TIMP-1 in the nonsurvivors (953 ± 184) compared with the survivors (4675 ± 1507). TIMP-2 was significantly higher (P < 0.001) in nonsurvivors than in the control group. Statistic analysis shows a correlation (Spearman Rank correlation, r = 0.7958) between serum levels of TIMP-1 and the severity of sepsis and the probability to die, but there was no correlation shown between the serum levels of MMP-3 and MMP-2.

Conclusion

Our results indicate that MMP-9, TIMP-2 and TIMP-1 may serve as sensitive and early markers for cell activation during the course of sepsis. Furthermore, TIMP-1 may be related to the prognosis and clinical outcome of septic patients.