IFNs

Interferons (IFNs) are cytokines produced by host cells in response to viral infection and other stimuli, acting to establish an antiviral state and modulate the immune response. They were named for their ability to interfere with viral replication and were first described in 1957 by Isaacs and Lindenmann. IFNs are divided into three main families based on receptor usage and function: Type I, Type II, and Type III. Type I includes multiple IFN-α subtypes, IFN-β, IFN-ω, and others, signaling through the IFN-α/β receptor (IFNAR). Type II consists solely of IFN-γ, signaling through the IFN-γ receptor (IFNGR). Type III comprises the IFN-λs (IFN-λ1/IL-29, IFN-λ2/IL-28A, IFN-λ3/IL-28B, IFN-λ4), signaling through the IFN-λ receptor complex (IFNLR1 with IL10R2).

Production and action: IFNs are produced by many cell types, with plasmacytoid dendritic cells as major sources of Type I. Upon receptor engagement, they activate the JAK-STAT signaling pathway, inducing hundreds of interferon-stimulated genes (ISGs) that inhibit viral replication, enhance antigen processing and presentation, and modulate both innate and adaptive immunity. Type I and III IFNs induce antiviral states in many cell types, while Type II IFN is more immunomodulatory, promoting macrophage activation and Th1 responses. The IFN response is a central component of innate immunity and can be antagonized by viral proteins.

Clinical use and considerations: recombinant IFNs have been used to treat certain diseases. Pegylated IFN-α was once standard therapy for chronic hepatitis B and C, though direct-acting antivirals have largely supplanted it. IFN-β is a standard treatment for relapsing forms of multiple sclerosis. IFN-λ is under investigation for mucosal infections and oncology. Common adverse effects include flu-like symptoms, cytopenias, and mood disturbances, necessitating careful monitoring.