Abstract
BackgroundThe pathogenesis of severe dengue has not been fully elucidated. The inflammatory response plays a critical role in the outcome of dengue disease.MethodsIn this study, we investigated the levels of 17 important inflammation mediators in plasma collected from mild or severe adult dengue patients at different time points to understand the contribution of inflammation to disease severity and to seek experimental evidence to optimize the existing clinical treatment strategies. Patients were simply classified as mild and severe dengue according to the 2009 WHO classification. Plasma was collected on day 3-5, 6-7, 8-10 and 14-17 of illness. Levels of 17 inflammation mediators including TNF-α, IL-1α, IFN-γ, IL-6, IFN-α, MIF, IL-10, IL-1RA, IL-8, IP-10, MCP-1, RANTES, GRO, eotaxin-1, sICAM-1 and sVCAM-1 were determined by a multiplex Luminex® system. Different trends of inflammation mediators throughout the disease were compared between mild and severe patients.ResultsInflammation mediators including IL-1α, IFN-γ, IL-10, IL-8, IP-10, MCP-1 and sVCAM-1 displayed significant differences on day 8-10 of illness between mild and severe dengue patients. Their concentrations were higher in severe patients than mild ones at the same time points. Moreover, those cytokines decreased gradually in mild patients but not in severe patients.ConclusionOur results revealed the coexistence of excessive inflammatory response and slow resolution of inflammation in severe adult dengue patients. Hence suppression and/or pro-resolution of inflammation could be a potential therapeutic approach for treatment of severe dengue.
Highlights
The pathogenesis of severe dengue has not been fully elucidated
We determined levels of 17 important inflammation mediators in plasma collected from mild or severe adult dengue patients at different time points to understand the contribution of inflammation to disease severity and to seek experimental evidence to optimize the existing clinical treatment strategies
With any of the following conditions, cases were diagnosed as severe disease: (1) plasma leakage leading to shock, respiratory distress, or both; (2) severe bleeding; and (3) severe organ impairment
Summary
The pathogenesis of severe dengue has not been fully elucidated. The inflammatory response plays a critical role in the outcome of dengue disease. Dengue, caused by dengue virus (DENV) infection, is considered as the most prevalent mosquito-borne viral disease in humans. All four serotypes of DENV (DENV-1 to DENV-4) can cause a spectrum of illness ranging from asymptomatic to life-threatening dengue shock syndrome [2]. Symptomatic disease includes two entities: mild and severe dengue according to the 2009 World. Mild dengue is a self-limited illness lasting about 7 days. Severe dengue, characterized by plasma leakage, may be fatal. Many efforts have been made to elucidate the underlying mechanisms of severe disease, it still remains unclear [4, 5]
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