Interferons

Interferons were discovered in 1957 by Isaacs and Lindermann who had observed that the supernatant of cultures inoculated with a virus contained a protein with the ability to protect adjacent cells against infection. Interferons are proteins in the family of low molecular weight cytokines produced by different types of cells. By binding to specific receptors, they regulate the proliferation, differentiation and functional activity of certain cells.

Interferons can be divided into three major types depending on the receptor through which they signal and certain structural, biochemical and antigenic differences:

• Type I consists of interferons with an α-spiral structure and includes interferon α, interferon β and the more recently described interferons ω, ε and κ:

– The interferon α group consists of at least fourteen proteins coded by non allelic genes located on chromosome 9 with a sequence homology of about 80%. The only difference between interferon α-2a and interferon α-2b is an amino acid. Interferon α is produced by leukocytes, macrophages, endothelial cells, tumour cells, keratinocytes and mesenchymal cells. It is produced in response to viral or bacterial infection and tumour cells.

– Interferon β is coded by a single gene, also located on chromosome 9, which shares 20% of its gene sequence with interferon a. Interferon b is produced by fibroblasts, endothelial cells, macrophages and epithelial cells in response to stimulation by a virus or foreign nucleic acids.

– Interferon ω is an embryonic interferon produced by T lymphocytes, which has no demonstrated clinical function. The characteristics of interferon ε, which is found in the cerebral tissues, and of interferon κ have not yet been fully elucidated.

• Type II consists of interferon γ which is coded by a single gene located on chromosome 12. It does not share gene homology with interferons α and β. It is produced by T lymphocytes after stimulation by foreign antigens and by natural killer (NK) cells.

• Type III consists of the interferon λ family which includes 3 proteins also called interleukins 28A, 28B and 29. They are coded by three genes on chromosome 19 and have more than 80% gene sequence homology with interferon α but also with the interleukin-10-related cytokines. Its structure is similar to that of interferon γ. It is mainly produced by dendritic cells and macrophages in response to viral or bacterial infections.

Interferons are produced by de novo synthesis and are then excreted in the extracellular liquid where they bind to three types of receptors:

• Type I which is present on most cell types and is believed to be common to interferons α and β. However, it is possible that interferons α and β may, in fact, have different receptors or different ways of interacting with this receptor.

• Type II, which is specific to interferon γ.

• Type III, which is specific to interferon λ. It triggers the same signalling pathway as the type I receptor but its location mainly at the surface of epithelial cells modifies its function.