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.

Serum levels of urokinase-type plasminogen activator in healthy dogs and oncologic canine patients

“…However, this hypothesis needs to be validated with a larger study. Nevertheless, similarly to what reported in human studies, canine uPA values seem to be independent of individual factors such as gender, age and weight [ 44 , 45 ].…”

Serum Urokinase-Type Plasminogen Activator Receptor Does Not Outperform C-Reactive Protein and Procalcitonin as an Early Marker of Severity of Acute Pancreatitis

“…The soluble uPAR is considered to be a non-specific marker of inflammation, including SIRS, both the one that is related and unrelated to infection. Yu et al [ 24 ] and Koch et al [ 20 ] reported positive associations between circulating uPAR and proinflammatory cytokines (IL-6, TNF-α), procalcitonin and CRP. Such correlations were also observed in our study.…”

“…Increased serum uPAR has been associated with various inflammatory states, particularly with sepsis and non-septic SIRS [ 17 , 20 , 21 , 22 ]. The correlation with severity of organ failure and mortality, together with the relative stability of plasma or serum concentrations, make uPAR a promising clinical biomarker in patients with SIRS [ 20 , 22 , 24 , 25 ], but so far has not been extensively studied in AP. Nonetheless, in 2017, Lipinski et al [ 26 ] showed a very high diagnostic accuracy of plasma uPAR for the prediction of SAP and fatal AP among patients of a tertiary referral hospital.…”

Urokinase-type plasminogen activator receptor as a predictor of poor outcome in patients with systemic inflammatory response syndrome

“…SIRS is an organic reaction generally associated with an infection (sepsis) or any situation that implies intense tissue damage with well-defined diagnostic criteria. [ 18 , 19 ] García-Fernández et al[ 20 ] have demonstrated that patients with SIRS, irrespective of the origin (infectious or noninfectious), show signs of intense endothelial damage and hypercoagulability throughout the process. The endothelial inflammation, together with a disturbance of hemostatic and tissue perfusion, leads to a progressive establishment of multiple organ dysfunction syndrome (MODS).…”

“…Qiu et al[ 22 ] identified that in a clinical situation, frequently characterized by fibrin occlusion of the microcirculation, the ability of polymorphonuclear leukocytes (PMN) to express uPA activity is diminished or absent. Yu et al[ 23 ] demonstrated that dramatically increased plasminogen activator inhibitor type 1 (PAI-1) levels during staphylococcal infection led to a reduction of metabolically active uPA levels. It has been well documented that uPA is required for generation of an adequate inflammatory response.…”