TY - JOUR A1 - Michels, Meta A1 - Japtok, Lukasz A1 - Alisjahbana, Bachti A1 - Wisaksana, Rudi A1 - Sumardi, Uun A1 - Puspita, Mita A1 - Kleuser, Burkhard A1 - de Mast, Quirijn A1 - van der Ven, Andre J. A. M. T1 - Decreased plasma levels of the endothelial protective sphingosine-1-phosphate are associated with dengue-induced plasma leakage JF - Journal of infection N2 - Background: A transient endothelial hyperpermeability is a hallmark of severe dengue infections. Sphingosine-1-phosphate (S1P) maintains vascular integrity and protects against plasma leakage. We related plasma S1P levels to dengue-induced plasma leakage and studied mechanisms that may underlie the decrease in S1P levels in dengue. Methods: We determined circulating levels of S1P in 44 Indonesian adults with acute dengue and related levels to plasma leakage, as determined by daily ultrasonography, and to levels of its chaperone apolipoprotein M, other lipoproteins and platelets. Results: Plasma S1P levels were decreased during dengue and patients with plasma leakage had lower median levels compared to those without (638 vs. 745 nM; p < 0.01). ApoM and other lipoprotein levels were also decreased during dengue, but did not correlate to S1P levels. Platelet counts correlated positively with S1P levels, but S1P levels were not higher in frozen-thawed platelet rich plasma, arguing against platelets as an important cellular source of S1P in dengue. Conclusions: Decreased plasma S1P levels during dengue are associated with plasma leakage. We speculate that decreased levels of ApoM underlies the lower S1P levels. Modulation of S1P levels and its receptors may be a novel therapeutic intervention to prevent plasma leakage in dengue. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved. KW - Sphingosine 1phosphate KW - Dengue KW - APOM protein KW - Human KW - Blood platelets Y1 - 2015 U6 - https://doi.org/10.1016/j.jinf.2015.06.014 SN - 0163-4453 SN - 1532-2742 VL - 71 IS - 4 SP - 480 EP - 487 PB - Elsevier CY - London ER -