Yleiskatsaus interferoneista 2017

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THE HISTORY OF INTERFERON RESEARCH

Interferons (IFN) are anti-viral cytokines that has been widely used clinically, especially against Hepatitis B virus (HBV) and Hepatitis C virus (HCV). The discovery of interferon is comparable to that of antibiotics, and may in fact be even more important given the fact that bacteria can be removed by filtering whereas viruses cannot. Interferon attracted worldwide attention after its discovery by Isaacs and Lindenmann in 1957, but initially researchers were only able to verify its existence and function and were unable to obtain enough amounts for further research and clinical applications. In 1986, 29 years after the discovery of interferon, the development of genetic engineering enabled the production of large quantities of high-quality interferon. This allowed for its wide spread application in both research and clinical settings, which ushered in a new era for interferon. Milestones in interferon research up to the year 2000 are summarized in table 1 [1].Table 1: Milestones of interferon research before 2000.
Years     Important events
1957     Virus-induced IFN
1964     IFN-mediated antiviral protection of mice
1967     Non-viral IFN inducers: ds RNA
1969     IFN-antitumor activity in mice
1970     IFNs: a family
1973     Clinical trials with impure IFNs
1975     IFNγ (immune IFN)
1976     IFN has antiviral effect in HBV-infected humans; Immunological effects of IFNs
1977     Human antitumor effects
1980     Purification, cloning, sequencing of IFN-α1, IFN-α2, IFN-β; Endothelial cell motility
1981     Clinical MS effects; Recombinant IFN cancer clinical trials
1982     IFN-γ cloned
1983     IFN gene promoter; First ISG cloned (2-5A synthetize)
1984     ISG promoters
1986     IFN-α2 FDA approval for hairy cell leukemia
1987     IFN anti angiogenic effects
1988     IFN-γ receptor cloned
1989     IRFs identified
1990     IFN-α2 FDA approval for HCV; Clinical pegylated IFN; IFNα receptor cloned
1992     STAT family of transcription factors; JAKs/STATs cloned
1993     IFN-β FDA approval for MS
1995     IFN-γ receptor complex crystal structure
1997     Toll receptor cloned
1998     Hundreds of ISGs
2000     IFN-γ FDA approval
 Since 2000, a major breakthrough in interferon research occurred in 2003 when two labs independently reported the discovery of a third type of interferon, IFN-λ with its three subtypes, IFNλ-1, IFNλ-2 and IFNλ-3 [2] (also known as IL-29, IL-28A, and IL-28B respectively [3]). These new interferons were later proven to have anti-viral effects, and were thus formally classified as type III interferons. Just seven years later, type III interferons were applied clinically for the first time when type III interferon drugs developed by two companies, BMS and Zymo Genetics, had entered phase three clinical trial. In January 2013, a new type of interferon, IFNL4 [4], was reported and soon produced a new upsurge in interferon research.