Document Detail

Angiopoietin-2 is increased in severe sepsis: correlation with inflammatory mediators.
MedLine Citation:
PMID:  17110873     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Angiopoietin (Ang)-2 is an endothelium-specific growth factor, regulated by proinflammatory stimuli, that destabilizes vascular endothelium and increases vascular leakage; consequently, Ang-2 may contribute to sepsis pathophysiology. We have studied 1) serum Ang-2 levels in critically-ill patients and investigated potential relationships with inflammatory mediators and indices of disease severity and 2) the effect of sepsis-related inflammatory mediators on Ang-2 production by lung endothelium in vitro. DESIGN: Prospective clinical study followed by cell culture studies. SETTING: General intensive care unit and research laboratory of a university hospital. SUBJECTS: Human and bovine lung microvascular endothelial cells and 61 patients (32 men). Patients were grouped according to their septic stage as having: no systemic inflammatory response syndrome (n = 6), systemic inflammatory response syndrome (n = 8), sepsis (n = 16), severe sepsis (n = 18), and septic shock (n = 13). INTERVENTIONS: Cells were exposed to lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6. MEASUREMENTS AND MAIN RESULTS: Patients' serum Ang-2 levels were significantly increased in severe sepsis as compared with patients with no systemic inflammatory response syndrome or sepsis (p < .05 by analysis of variance). Positive linear relationships were observed with: serum tumor necrosis factor-alpha (rs = 0.654, p < .001), serum interleukin-6 (rs = 0.464, p < .001), Acute Physiology and Chronic Health Evaluation II score (rs = 0.387, p < .001), and Sequential Organ Failure Assessment score (rs = 0.428, p < .001). Multiple regression analysis revealed that serum Ang-2 is mostly related to serum tumor necrosis factor-alpha and severe sepsis. Treatment of human lung microvascular endothelial cells with all mediators resulted in a concentration-dependent Ang-2 reduction. Treatment of bovine lung microvascular endothelial cells with lipopolysaccharide and tumor necrosis factor-alpha increased Ang-2 release, and interleukin-6 reduced basal Ang-2 levels. CONCLUSIONS: First, patients' serum Ang-2 levels are increased during severe sepsis and associated with disease severity. The strong relationship of serum Ang-2 with serum tumor necrosis factor-alpha suggests that the latter may participate in the regulation of Ang-2 production in sepsis. Second, inflammatory mediators reduce Ang-2 release from human lung microvascular endothelial cells, implying that this vascular bed may not be the source of increased Ang-2 in human sepsis.
Stylianos E Orfanos; Anastasia Kotanidou; Constantinos Glynos; Chariclea Athanasiou; Stelios Tsigkos; Ioanna Dimopoulou; Christina Sotiropoulou; Spyros Zakynthinos; Apostolos Armaganidis; Andreas Papapetropoulos; Charis Roussos
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  35     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-01     Completed Date:  2007-01-19     Revised Date:  2007-04-12    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  199-206     Citation Subset:  AIM; IM    
Second Department of Critical Care, Attikon University Hospital, University of Athens Medical School, 1 Rimini Street, Haidari, Athens 124 62, Greece.
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MeSH Terms
Analysis of Variance
Angiopoietin-2* / blood,  immunology
Case-Control Studies
Critical Illness
Endothelium, Vascular / cytology,  immunology
Hospitals, University
Inflammation Mediators* / blood,  immunology
Interleukin-6 / blood,  immunology
Linear Models
Lung / blood supply
Middle Aged
Prospective Studies
Regression Analysis
Sepsis / blood*,  classification,  immunology*
Severity of Illness Index
Systemic Inflammatory Response Syndrome / blood*,  classification,  immunology
Tumor Necrosis Factor-alpha / blood,  immunology
Reg. No./Substance:
0/Angiopoietin-2; 0/Inflammation Mediators; 0/Interleukin-6; 0/Tumor Necrosis Factor-alpha
Erratum In:
Crit Care Med. 2007 Apr;35(4):1224

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