Interferons are signaling proteins produced by host cells in response to pathogens like viruses, bacteria, parasites, and tumor cells. These proteins play a crucial role in the body’s innate immune system, acting as a first line of defense. They are named for their ability to “interfere” with viral replication, helping to protect healthy cells from infection. Interferons coordinate both innate and adaptive immune responses.
Main Classes of Interferons
Interferons are broadly categorized into three main classes: Type I, Type II, and Type III, each with distinct characteristics and functions.
Type I interferons include subtypes such as:
Interferon-alpha (IFN-α)
Interferon-beta (IFN-β)
Interferon-epsilon (IFN-ε)
Interferon-kappa (IFN-κ)
Interferon-omega (IFN-ω)
Most nucleated cells, including specialized immune cells like plasmacytoid dendritic cells and fibroblasts, produce them, typically in response to viral infections. Their role is to initiate early antiviral responses by signaling to nearby uninfected cells, establishing an antiviral state.
Type II interferons consist of a single member, interferon-gamma (IFN-γ). Unlike Type I interferons, IFN-γ is mainly produced by immune cells, particularly activated T cells and natural killer (NK) cells, and its production is often triggered by cytokines. IFN-γ regulates and activates other immune cells, such as macrophages, to combat intracellular pathogens and enhance immune surveillance. It also plays a significant role in immune and inflammatory responses.
Type III interferons, also known as interferon-lambda (IFN-λ), include subtypes like:
IFN-λ1
IFN-λ2
IFN-λ3
IFN-λ4
Epithelial cells and some immune cells predominantly produce these, particularly at mucosal surfaces like the respiratory and gastrointestinal tracts. Type III interferons contribute to antiviral defenses at sites of external pathogen contact. While their actions overlap with Type I interferons, they act through a distinct receptor complex.
How Interferons Operate
Interferons exert their effects by binding to specific receptors on target cells. This binding initiates intracellular signaling events, activating the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. This pathway leads to the activation of transcription factors that move into the cell’s nucleus.
Once in the nucleus, these transcription factors regulate hundreds of interferon-stimulated genes (ISGs). Proteins from these ISGs inhibit viral replication at various stages of the viral life cycle. This process induces an “antiviral state” in treated and neighboring cells. Beyond direct antiviral actions, interferons also modulate immune responses by activating immune cells like natural killer cells and macrophages, and by enhancing the presentation of antigens to T cells.
Therapeutic Uses of Interferons
Synthetic interferons have found various applications in medicine due to their antiviral, antiproliferative, and immunomodulatory properties.
Interferon-alpha (IFN-α) treats chronic viral infections like Hepatitis B and C, though newer treatments exist. It also treats certain cancers, including:
Hairy cell leukemia
Kaposi sarcoma
Malignant melanoma
Renal cell carcinoma
This is achieved by stimulating immune cells and slowing cancer cell growth. While once a standard treatment for chronic myeloid leukemia, newer targeted therapies have largely replaced it.
Interferon-beta (IFN-β) is a common treatment for various forms of multiple sclerosis (MS), an autoimmune disorder. It reduces inflammation in the brain and spinal cord, lessening relapse frequency and slowing disease progression. IFN-β has a long-established safety profile, making it a primary option for many patients with relapsing MS.
Interferon-gamma (IFN-γ) treats specific conditions like chronic granulomatous disease, an immune system disorder, and severe malignant osteopetrosis, a bone disease. Interferon-lambda (IFN-λ) is under investigation for treating viral infections, particularly those affecting mucosal surfaces, but has no FDA-approved clinical uses yet.