title: Hypertonic saline reduces vascular leakage in a mouse model of severe dengue.
abstract: Dengue (DEN) is a mosquito-borne viral disease and represents a serious public health threat and an economical burden throughout the tropics. Dengue clinical manifestations range from mild acute febrile illness to severe DEN hemorrhagic fever/DEN shock syndrome (DHF/DSS). Currently, resuscitation with large volumes of isotonic fluid remains the gold standard of care for DEN patients who develop vascular leakage and shock. Here, we investigated the ability of small volume of hypertonic saline (HTS) suspensions to control vascular permeability in a mouse model of severe DEN associated with vascular leakage. Several HTS treatment regimens were considered and our results indicated that a single bolus of 7.5% NaCl at 4 mL per kg of body weight administered at the onset of detectable vascular leakage rapidly and significantly reduced vascular leak for several days after injection. This transient reduction of vascular leakage correlated with reduced intestine and liver damage with restoration of the hepatic functions, and resulted in delayed death of the infected animals. Mechanistically, we showed that HTS did not directly impact on the viral titers but resulted in lower immune cells counts and decreased systemic levels of soluble mediators involved in vascular permeability. In addition, we demonstrated that neutrophils do not play a critical role in DEN-associated vascular leakage and that the therapeutic effect of HTS is not mediated by its impact on the neutrophil counts. Together our data indicate that HTS treatment can transiently but rapidly reduce dengue-associated vascular leakage, and support the findings of a recent clinical trial which evaluated the efficacy of a hypertonic suspension to impact on vascular permeability in DSS children.
authors: Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore, Singapore.
authors: Grace Kai Xin
authors: GK
authors: Tan
authors: Jowin Kai Wei
authors: JK
authors: Ng
authors: Kar Wai
authors: KW
authors: Tan
authors: Veronique
authors: V
authors: Angeli
authors: Shabbir
authors: S
authors: Moochhala
authors: Eng Eong
authors: EE
authors: Ooi
authors: Sylvie
authors: S
authors: Alonso
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D003715:Dengue / Q000188:drug therapy*; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000097:blood; D051379:Mice; D009504:Neutrophils / Q000502:physiology; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D018836:Inflammation Mediators; D012462:Saline Solution, Hypertonic
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