Hypertonic saline reduces vascular leakage in a mouse model of severe dengue
| Autor: | Eng Eong Ooi, Shabbir Moochhala, Kar Wai Tan, Grace K. Tan, Jowin Kai Wei Ng, Veronique Angeli, Sylvie Alonso |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Viral Diseases
medicine.medical_specialty Resuscitation Critical Care and Emergency Medicine Mouse Neutrophils Fluid Management lcsh:Medicine Vascular permeability Gastroenterology Dengue Fever Dengue fever Capillary Permeability Dengue Mice Model Organisms Immune system Internal medicine medicine Animals lcsh:Science Biology Saline Solution Hypertonic Viral Hemorrhagic Fevers Multidisciplinary business.industry Therapeutic effect lcsh:R Animal Models medicine.disease Hypertonic saline Disease Models Animal Infectious Diseases Shock (circulatory) Immunology Medicine Tonicity lcsh:Q Inflammation Mediators medicine.symptom Infectious Disease Modeling business Research Article Neglected Tropical Diseases |
| Zdroj: | PLoS ONE, Vol 8, Iss 4, p e61621 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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