@article{3115502,
    title = "Angiopoietin-2 is increased in severe sepsis: Correlation with
inflammatory mediators",
    author = "Orfanos, Stylianos E. and Kotanidou, Anastasia and Glynos, Constantinos and and Athanasiou, Chariclea and Tsigkos, Stelios and Dimopoulou, Ioanna and and Sotiropoulou, Christina and Zakynthinos, Spyros and Armaganidis, and Apostolos and Papapetropoulos, Andreas and Roussos, Charis",
    journal = "Pediatric Critical Care Medicine",
    year = "2007",
    volume = "35",
    number = "1",
    pages = "199-206",
    publisher = "Lippincott, Williams & Wilkins",
    issn = "1529-7535",
    doi = "10.1097/01.CCM.0000251640.77679.D7",
    keywords = "lung; endothelium; sepsis; angiopoietin-2; tumor necrosis factor-alpha;
interleukin-6",
    abstract = "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 (r(s) = 0.654, p <.001), serum interleukin-6
(r(s) = 0.464, p <.001), Acute Physiology and Chronic Health Evaluation
II score (r(s) = 0.387, p <.001), and Sequential Organ Failure
Assessment score (r(s) = 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."
}