Decreased serum concentrations of sphingosine-1-phosphate in sepsis.
BACKGROUND
Sphingosine-1-phosphate (S1P) is a signaling lipid that regulates pathophysiological processes involved in sepsis progression, including endothelial permeability, cytokine release, and vascular tone. The aim of this study was to investigate whether serum-S1P concentrations are associated with disease severity in patients with sepsis.


METHODS
This single-center prospective-observational study includes 100 patients with systemic inflammatory response syndrome (SIRS) plus infection (n = 40), severe sepsis (n = 30), or septic shock (n = 30) and 214 healthy blood donors as controls. Serum-S1P was measured by mass spectrometry. Blood parameters, including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), lactate, and white blood cells (WBCs), were determined by routine assays. The Sequential Organ Failure Assessment (SOFA) score was generated and used to evaluate disease severity.


RESULTS
Serum-S1P concentrations were lower in patients than in controls (P < 0.01), and the greatest difference was between the control and the septic shock groups (P < 0.01). Serum-S1P levels were inversely correlated with disease severity as determined by the SOFA score (P < 0.01) as well as with IL-6, PCT, CRP, creatinine, lactate, and fluid balance. A receiver operating characteristic analysis for the presence or absence of septic shock revealed equally high sensitivity and specificity for S1P compared with the SOFA score. In a multivariate logistic regression model calculated for prediction of septic shock, S1P emerged as the strongest predictor (P < 0.001).


CONCLUSIONS
In patients with sepsis, serum-S1P levels are dramatically decreased and are inversely associated with disease severity. Since S1P is a potent regulator of endothelial integrity, low S1P levels may contribute to capillary leakage, impaired tissue perfusion, and organ failure in sepsis.
Department of Anaesthesiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. m.winkler@uke.de.
Martin Sebastian
MS
Winkler
Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. nierhaus@uke.de.
Axel
A
Nierhaus
Department of Anaesthesiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. m.holzmann@uke.de.
Maximilian
M
Holzmann
Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. e.mudersbach@uke.de.
Eileen
E
Mudersbach
Department of Anaesthesiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. toni.b.90@gmx.de.
Antonia
A
Bauer
Department of Anaesthesiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. linda@robbe-online.de.
Linda
L
Robbe
Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. corinne.zahrte@gmail.com.
Corinne
C
Zahrte
Institute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. maria.geffken@uke.de.
Maria
M
Geffken
Institute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. s.peine@uke.de.
Sven
S
Peine
Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. schwedhelm@uke.de.
Edzard
E
Schwedhelm
Clinic and Polyclinic for Vascular Medicine, University Heart Center, Martinistr. 52, 20246, Hamburg, Germany. g.daum@uke.de.
Guenter
G
Daum
Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. s.kluge@uke.de.
Stefan
S
Kluge
Department of Anaesthesiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. c.zoellner@uke.de.
Christian
C
Zoellner
D000328:Adult; D005260:Female; D005858:Germany; D006801:Humans; D008246:Lysophospholipids / Q000097:blood* / Q000172:deficiency; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000401:mortality*; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood / Q000401:mortality* / Q000628:therapy; D012720:Severity of Illness Index; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood / Q000172:deficiency
D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine