Induction of Antiviral Factors by IFN-α 2a is Time and Dose Dependent

Interferon alpha is an effective cytokine in viral infections, where it has various roles in immune function. The use of this antiviral agent in the treatment of viral infections and even cancers is common, although, the beneficial effects of this antiviral agent in high doses can be associated with side effects that limit its use. In this project, we tried to investigate the effects of different doses and timing of interferon alpha treatment on the expression of downstream interferon signaling genes and evaluation of the antiviral effects in patients with chronic hepatitis C.

Peripheral blood mononuclear cells (PBMCs) were isolated from treatment-naive HCV-infected patients. The cells were treated with different doses of Interferon alpha 2a (IFN-α 2a) and the mRNA expression of target genes (ISG15, MXA, PKR and OAS) at different time points was evaluated by Real Time PCR. The levels of ISG15 and OAS were measured in culture supernatant using ELISA and the level of HCV NS5A in chronic HCV patients was measured by flow cytometry.

Our results showed that IFN-α 2a effect on the expression of antiviral proteins was dependent on dose and time of administrated IFN-α.

This finding indicates that IFN-α should be used at optimal dose to achieve the best efficiency and established balance between antiviral and anti-tumor effects of IFN-α with fewer side effects.