Serum Levels of Trace Elements, Proinflammatory Cytokines and Nitric Oxide in NS1 Positive Cases in Acute Dengue Virus Infections

Abstract

Background: Dengue virus (DENV) infection is characterized by severe vascular complications viz. dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) in a perceptible population justifying the need for an early marker that could reliably predict such adverse outcomes. A nonstructural protein antigen of DENV termed NS1 antigen that is detectable during acute stage of DENV infection was evaluated to find out its association with alteration of some trace element levels viz. zinc (Zn), selenium (Se), iron (Fe), copper (Cu) and magnesium (Mg), levels of nitrite (the stable product of NO), as well as levels of interferon γ (IFN-γ), interleukin-1 β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-12 (IL-12) and tumor necrosis factor α (TNF-α) in acute stage of DENV infection to find out if any alteration of these parameters associated with NS1 positivity could strengthen its predictive value for development of pathogenic consequences following acute DENV infection.

Methods: Estimation of concentrations of trace elements by flame atomic absorption spectrometry (FAAS) method, while the levels of nitrite and citrulline by Griess reaction and cytokine estimation was done by enzyme-linked immunosorbent assay (ELISA) method.

Results: There was significant depression of Cu levels in cases positive for NS1 antigen alone (n = 50) or in combination with IgM positivity (n = 15) compared to cases with IgM positivity alone (n = 50), other febrile illness (OFI) group (n = 50) and both rural and urban healthy controls (n = 50 each). Serum level of Se was increased in all the serological subgroups of acute DENV cases, in the OFI group as well as in healthy rural controls compared to urban controls. There was significant depression in nitrite level in NS1 positive cases regardless of associated IgM positivity. The reduced serum nitrite levels in NS1 positive cases, with or without associated IgM positivity, correlated positively with decrease in serum Cu level and negatively with increase in TNF-α level in the corresponding subgroups.

Conclusions: The present study revealed altered status of some markers in serum associated with NS1 positivity that may strengthen the validity of NS1 positivity as a predictive marker for development of complications thus help in timely management of DENV infection.




Clin Infect Immun. 2018;3(1):9-15
doi: https://doi.org/10.14740/cii47w