<i>In vitro</i> immunomodulatory effect of siRNA complexes in the influenza infection

Abstract

About 1.2 billion cases of influenza infection with up to 5 million cases of severe disease and up to 650,000 deaths from influenza and its complications are registered annually worldwide. High rates of morbidity and mortality are attributed to immunomodulatory properties of some proteins produced by the influenza viruses. Among these proteins, NS-1 is the most studied. One of its main functions is to disrupt the functioning of interferon-mediated defense mechanisms of the body thus causing suppressed production of different components of humoral immunity, which leads to an insufficiency of the immune response. It is known that miRNAs directed to cellular genes, which are involved in the process of viral reproduction, showing a pronounced antiviral activity. At the same time, only few studies have been focused on evaluation of their immunotropic effects. Therefore, the aim of our study was to quantify the concentrations of IFNα, IFNγ, TNFα and IL-10 cytokines as a result of complex suppression of the cellular FLT4, Nup98 and Nup205 gene activity, whose expression products play an important role in the reproduction of the influenza virus.
 We have shown that the use of siRNA complexes also leads to an increase in the IFNα, IFNγ, TNFα and IL-10 concentrations. IL-10 production is absent on the first day after infection, but begins to increase on the second and third days. Moreover, in some cases, there is an increase in IFNα and IFNγ concentration on the first day after infection followed by decrease in their concentrations by the third day. This finding indicates that, upon supplement of the siRNA complexes, the cytokine profile is normalized under the influence of IL-10.