Increase of circulating endocan over sepsis follow-up is associated with progression into organ dysfunction

Abstract

How circulating inflammatory mediators change upon sepsis progression has not been studied. We studied the follow-up changes of circulating vasoactive peptides and cytokines until the improvement or the worsening of a patient and progression into specific organ dysfunctions. In a prospective study, concentrations of tumor necrosis factor-alpha (TNFα), interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), endocan and angiopoietin-2 (Ang-2) were measured in serum by an enzyme immunoassay in 175 patients at baseline; this was repeated within 24 h upon progression into new organ dysfunction (n = 141) or improvement (n = 34). Endocan and Ang-2 were the only parameters that were significantly increased among patients who worsened. Any increase of endocan was associated with worsening with odds ratio 16.65 (p < 0.0001). This increase was independently associated with progression into acute respiratory distress syndrome (ARDS) as shown after logistic regression analysis (odds ratio 2.91, p: 0.002). Changes of circulating cytokines do not mediate worsening of the critically ill patients. Instead endocan and Ang2 are increased and this may be interpreted as a key-playing role in the pathogenesis of ARDS and septic shock. Any increase of endocan is a surrogate of worsening of the clinical course.

Angiopoietin-2 Levels as Predictors of Outcome in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome

“…Endocan is a vasoactive and endothelial-derived molecule that is mainly produced in the event of ARDS. Since previous studies have also associated this biomarker with the progression of septic patients into organ dysfunction [ 14 ], it is not surprising that levels greater than 13 ng/ml are predictive for failure to withdrawal from mechanical ventilation.…”

“…Former studies have shown elevated plasma endocan concentrations in patients with sepsis [ 12 ] and have associated them with disease severity and progression [ 13 ]. Other studies have identified plasma endocan levels as an independent predictor in septic patients progressing into ARDS [ 14 ] and have explored its potential as a biomarker to predict disease severity and mortality in ARDS [ 15 ]. Nonetheless, the full value of endocan as a biomarker and the significance of its levels in the endothelial lining fluid (ELF) in ARDS have not yet been studied.…”

Endocan, sepsis, pneumonia, and acute respiratory distress syndrome

“…Endothelial cells play a key role in the pathogenesis of sepsis by producing cytokines and chemotactic agents, and by expressing surface adhesion molecules, which induce migration of circulating leukocytes into tissues. Indeed, both endocan and angiopoietin-2 are endothelial-specific biomarkers which increase during sepsis, worsening into multiple organ dysfunction syndrome (MODS), and decrease when sepsis improves [ 47 ]. Endocan showed correlation with VCAM-1 and E-selectin but not with ICAM-1 [ 48 ].…”

“…A total of 446 patients with or without ARDS at ICU admission have been tested currently for endocan. In polytrauma, severe sepsis, or septic shock patients without ARDS at admission, high levels of endocan were found predominantly in patients who did not develop ARDS [ 47 , 56 – 58 ]. Consistently, blood endocan levels below 5.5 ng/ml in these critically ill patients without ARDS at admission were associated with a high risk of ARDS occurrence within 3 days (Table 4 ).…”

Role of the extracellular matrix in the genesis of ventilator-induced lung injury

“…Endocan, a DS-PG synthesized and secreted by endothelial cells, is metabolized mainly by proteases throughout the lung and by inflammatory cells. Endocan levels are increased in the serum of patients with ARDS, pneumonia, and septic shock, and any increase of this PG in serum is a surrogate marker of worsening clinical course towards organ dysfunction [17,18]. Thus, analysis of PG fragments from the basal membrane of the alveolar epithelium and endothelium and from the interstitium might be helpful in the near future as early phase markers of lung injury in previously uninjured or injured lungs.…”