Prognostic significance of urokinase-type plasminogen activator and its receptor in patients with systemic inflammatory response syndrome

Abstract

BACKGROUND: This study aimed to determine the plasma levels of urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), D-dimer, IL-6 and TNF-α, and observe the relations among uPA, uPAR, D-dimer, IL-6 and TNF-α in patients with systemic infl ammatory response syndrome (SIRS). METHODS: A prospective, clinical case-control study was conducted in patients with SIRS at age of more than 55 years old treated during 2008-2010 at Wuhan Central Hospital. Venous blood samples were collected by routine venipuncture. Eighty-five patients were divided into two groups according to diagnostic criteria of SIRS: SIRS patients from intensive care units (n=50), and non-SIRS patients from medical wards (n=35). Thirty healthy blood donors who visited the General Health Check-up Division at Wuhan Central Hospital served as controls. Excluded from the study were (1) those patients with pregnancy; (2) those with cancer; (3) those died after admission into the ICU in 7 days; (4) those received cardiopulmonary resuscitation; (5) those who had previous blood system diseases; and (6) those with SIRS before admission into the ICU. The levels of uPA, uPAR, D-D, IL-6 and TNF-α in blood were detected by commercial enzyme-linked immunosorbent assay (ELISA) kit. The data were analyzed using SPSS version 17.0 and expressed as mean ± standard. Student's t test and the Mann-Whitney U test were used in the analysis. The relations of uPA, uPAR and D-dimer, IL-6 TNF-α levels were analyzed using Spearman's rank-order correlation coeffi cient test. RESULTS: The plasma levels of uPA , uPAR, D-dimer,IL-6 and TNF-α in the patients with SIRS were obviously higher than those in the non-SIRS patients and controls (P<0.001). Correlation analysis showed a positive correlation between uPAR and IL-6 levels (r=0.395, P=0.004) and between uPAR and TNF-α levels (r=0.606, P<0.001), but no correlation between uPAR and D-dimer levels (r=0.069, P=0.632). No correlation was observed between uPA, D-dimer, IL-6 and TNF-α levels (P>0.05). The establishment of ROC curve was based on the levels of uPAR, D-dimer, IL-6 and TNF-α in 24 hours for the diagnosis of multiple organ dysfunction syndrome (MODS), and the ROC areas under the curve were 0.76, 0.58, 0.86 and 0.83, respectively. CONCLUSIONS: uPA and uPAR play a major role in patients with SIRS in the process of coagulation disorder, but the mechanism of SIRS is not the same. uPAR may play a central role in the development of SIRS to MODS.