Matrix-metalloproteinases and their inhibitors are elevated in severe sepsis: Prognostic value of TIMP-1 in severe sepsis

Abstract

The enzyme group of matrix metalloproteinases (MMPs) and their inhibitors, so-called tissue inhibitors of matrix-metalloproteinases (TIMPs), are crucial mediators responsible for wound repair after parenchymal damage. Little is known about the role of MMPs and TIMPs in severe sepsis. The aim of the present study was therefore to investigate their levels in patients with severe sepsis and to examine their association with prognosis. MMP-2, MMP-9, TIMP-1, TIMP-2 and interleukin-6 (IL-6) plasma levels were measured by ELISA methods in 37 patients on day 1 of severe sepsis. 37 healthy volunteers served as controls. Levels of MMP-9, TIMP-1, TIMP-2 and IL-6 in septic patients were significantly higher compared to healthy controls (p<0.001), whereas MMP-2 levels were not different in patients and controls. TIMP-1 levels were significantly higher in non-survivors (4675+/-435 ng/ml, mean+/-SEM) compared to survivors of severe sepsis (3201+/-249 ng/ml; p<0.01). Septic patients with TIMP-1 values >3200 ng/ml were 4.5 times more likely to die than patients with lower values (RR = 4.5; 95% CI 1.14-17.6, p = 0.014). Our results indicate that MMP-9, TIMP-2 and TIMP-1 are elevated in severe sepsis. Furthermore, TIMP-1 may serve as a useful laboratory marker to predict the clinical outcome of patients presenting with severe sepsis.

Matrix Metalloproteinases as Drug Targets in Infections Caused by Gram-Negative Bacteria and in Septic Shock

“…Patients with TIMP-1 levels of Ͼ3,200 ng/ml were 4.5 times more likely to die than those with lower levels. The researchers concluded that TIMP-1 might serve as a useful laboratory marker for predicting the clinical outcome for patients with severe sepsis (44). High levels of neutrophil MMP-8 also were found in the peritoneal fluid of critically ill patients with secondary peritonitis (43).…”

Proteins involved in extracellular matrix dynamics are associated with respiratory syncytial virus disease severity

“…MMP activity has been implicated in the severity of a range of diseases including infectious diseases. For example, TIMP-1 levels are higher in nonsurvivors compared with survivors of severe sepsis [25]. Furthermore, TIMP-1-deficient mice show enhanced resistance to pulmonary infection with Pseudomonas aeruginosa [26], indicating that inhibition of MMP activity is related to a reduced capacity to clear infection.…”

Procalcitonin in sepsis and bacterial infections

“…55 Levels of both matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) were significantly elevated in a series of 37 patients with severe sepsis compared to similar number of healthy controls, and TIMP was found to be at higher lev-els in those who died, compared to the survivors. 56 Other markers like IL-6,IL-8,IL-18, transforming growth factor -1, interferon-, resistin, cluster of differentiation 64 (CD-64), serum lactate etc., have also been evaluated in various studies 30,[57][58][59] to find out their diagnostic and prognostic potentials in sepsis with variable results.…”