Interferon therapy: From cell signaling to haematological side effects

Interferons (IFNs) regulate a number of key biological functions in innate immune response, including antiviral activity, immunomodulatory tasks as well as cell growth regulation. The diverse effects of the type I IFNs are of differential therapeutic importance: In cancer therapy, an anti-proliferative effect may be beneficial whereas in the therapy of viral infection, the same anti-proliferative effect would lead to dose limiting bone marrow suppression.

IFN-α binds to interferon receptor 1 and 2 and forms a ternary complex that includes both receptor chains instigating signaling. Two types of signals are initiated and reflect on the production of secondary cytokines: IFN-γ mediating the antiviral activity on one hand, and interleukin 6, interleukin 4, interleukin 10 and IFN-inducible suppressive proteins mediating the anti-proliferative response on the other.

All pegylated interferons are not alike in terms of cytokine response. Based on their 3-D conformation, the differential ability of the different IFNs to bind preferentially to subunits of their receptor determines their therapeutic potentials, balancing their antiviral response on one hand and their anti-proliferative potential on the other and echoing on their haematological side effect profile.