Human interferon alpha (IFN-alpha)

Human interferon alpha (IFN-alpha) consists of a group of 13 closely related Type I interferon subtypes (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, and IFNA21) that are essential components of the innate immune system (UniProt, P01562). These proteins are primarily produced by plasmacytoid dendritic cells and leukocytes in response to viral infections and other danger signals. All IFN-alpha subtypes signal through a common heterodimeric receptor, IFNAR1/IFNAR2, which triggers the JAK-STAT pathway to induce the expression of hundreds of interferon-stimulated genes (ISGs) that inhibit viral replication and suppress cell proliferation (PubMed, PMC4044415). Historically, recombinant IFN-alpha subtypes have been used as therapeutic agonists to treat chronic viral hepatitis and various malignancies, such as hairy cell leukemia and melanoma (DrugBank, DB00105). However, chronic overproduction of IFN-alpha is a key driver in the pathogenesis of systemic lupus erythematosus (SLE), leading to the development of therapeutic antibodies designed to neutralize these cytokines (PubMed, PMC3491691). The clinical application of IFN-alpha is frequently complicated by a high incidence of adverse effects, most notably severe flu-like symptoms and significant neuropsychiatric morbidity (StatPearls, NBK541031).

Other names

IFNAType I interferonLeukocyte interferonInterferon alphaIFN-α

Agonism of the Type I interferon receptor (IFNAR1/IFNAR2) complex to activate the JAK-STAT signaling pathway, leading to the induction of interferon-stimulated genes (ISGs) for antiviral and antitumor effects (PubMed, PMC4044415). Alternatively, antagonism via neutralizing monoclonal antibodies that bind to IFN-alpha subtypes to prevent receptor activation in autoimmune diseases (PubMed, PMC3491691).