Introduction of Type I Interferon

Type I interferons are a large group of structurally similar cytokines, in humans including more than 13 different members of IFNα as well as IFNβ, IFNε, IFNκ and IFNω. The genes encoding type I interferons are clustered in one locus on the same chromosome (chromosome 9 in humans and chromosome 4 in mice), and they have been suggested to have diverged from a common ancestor, with the IFNβ gene being the primordial gene. Despite their seemingly broad range of amino-acid homologies, all type I IFNs signal through a common heterodimeric receptor composed of low- (IFNAR1) and high-affinity (IFNAR2) receptor components.

More than 50 years after their discovery, type I interferons have been included in our therapeutic armamentarium and are indicated for several disease entities. Firstly, type I interferons are widely used for the treatment of chronic viral infections, mainly by hepatitis B virus and hepatitis C virus. Type I interferons have also been used in the treatment of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), with more success in animal models than in the clinic. In addition to the above-described beneficial effects in infections, in malignancies and in some autoimmune/inflammatory diseases, there is evidence that type I interferons can also be detrimental for the host by promoting autoimmunity, inflammation and interferon treatment-related toxicities in a context-dependent manner.