A bit of a biology ramble – Interferon

 

Interferon is the name given to a group of proteins that act on the body’s immune response, they inhibit viral infections, stimulate the immune system and regulating many cell functions.

Host cells produce interferon; they then act as signalling proteins. For example, in a typical scenario, a virus-infected cell will release interferon causing nearby cells to heighten their anti-viral defences.

Interferon belongs to a larger group of cells called Cytokines; these are small proteins, which on release affect the behaviour of the cells around them. Interferon has the capability to inhibit cell growth and slow cell division, which is why their use against cancer is so promising.

Interferon basically interferes (hence the name) with viral cells, the first interferon was discovered in 1957 by Alick Isaacs and Jean Lindenmann. During their investigation, the two scientists found that virus-infected cells secrete a special protein that causes both infected and non-infected cells to produce other proteins that prevent viruses from replicating. Interferon can be split into alpha, beta, gamma, omega and tau depending on their molecular structure. Further to that, they can also be split into type I or II, depending on their amino acid make up, gamma is the only known interferon to have a type II structure.

Initially they thought there was only one form of interferon, to date, more than 20 have been discovered (mostly in the form of Alpha, only few Beta, Gamma, and only recently; Omega and Tau).

Type I interferon cells are known primarily for their ability to make nearby cells resistant to viral infections. Type II is known mainly for overall immune system regulation. Type I interferon can be produced by almost every cell in the body, (Alpha interferon is produced by white blood cells other than lymphocytes, Beta interferon by fibroblasts,) while the type II interferon-Gamma is produced only by specialised cells in the immune system known as T lymphocytes and natural killer cells.

As well as fighting and inhibiting the transcription of viral cells, interferon can also stimulate the production (or control) of other cells involved with the immune system. For example, interferon alpha can stimulate or inhibit the production of B Lymphocytes, for fighting infection, and Gamma can induce the production of a class of T lymphocytes known as suppressor CD8 cells, which can inhibit B cells from making antibodies. (Interferon Gamma can also induce the production of various other infection fighting cells, to help macropages, another form of white blood cell, to function more effectively against virus, bacteria and parasites).

Basically they are pretty versatile, useful, adaptable little proteins.

In 1986, interferon-alpha became the first interferon to be approved by the Food and Drug Administration (FDA) as a viable therapy, in this case, for hairy-cell leukaemia. (Directly injected into the bloodstream).

In January 2001, the Food and Drug Administration (FDA) approved the use of PEGylated interferon-alpha in the USA; in this formulation, PEGylated interferon-alpha-2b polyethylene glycol is linked to the interferon molecule to make the interferon last longer in the body. Approval for PEGylated interferon-alpha-2a followed in October 2002. Meaning the injections only have to be administered once a week, rather than 2-3 times, as per conventional interferon alpha.

This drug is approved around the world for the treatment of chronic hepatitis C and has recently been approved (in the EU, U.S., China and many other countries) for the treatment of chronic hepatitis B. It is also used in the treatment of certain T-cell lymphomas. Interferon Beta is also used in the treatment of MS.

In the UK, conventional interferon alpha (usually Roferon or Intron) is used in the treatment of many illnesses (MPNs, various Lymphomas, various melanomas, Hepatitis A and B; sometimes in conjunction with Ribavirin) this is an injection administered subcutaneously 2-3 times a week, usually with substantial side effects.

Pegylated interferon (in many cases) is only available if conventional interferon can be proven to be intolerable (due to side effects) and then is assessed on a patient by patient basis (depending on governing bodies, and funding available). This is probably because this drug costs approximately 3 times as much per year per patient than the non-Pegylated version.

What is interesting; is the application of Interferon in the treatment of MPNs, (myeloproliferative neoplasm -MPNs are classed by the World Health Organization as blood cancers because the bone marrow is producing blood cells in an uncontrolled way). These fall into three categories – ET, PV and MF. (essential thrombosythemia, polycythaemia vera and myelofibrosis).

 

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 “(Interferon) induces complete hematologic remissions in patients with myeloproliferative neoplasms…” Stressing the importance of low dose IFN started relatively early in the course of MPNs, the promise of interferon in PV is “significant clinical, hematologic, morphologic and molecular response, this last demonstrated by reduction of the JAK2 allele burden. The changes are durable, lasting long after discontinuation of treatment. In ET platelet counts drop rapidly and in primary MF interferon “has restored normal blood counts, reduced splenomegaly and induced morphologic marrow remissions.” (“Interferon and the treatment of polycythemia vera, essential thrombocythemia and myelofibrosis,” (Expert-Reviews – Hematology [2013) by Richard Silver (Weill-Cornell), Jean-Jacques Kiladjian( Hopital Saint-Louis, Centre d’Investigations Cliniques, Paris)

So, there is promising evidence; that through early treatment with interferon, many patients of MPNs, could potentially achieve long term remission, even after treatment ends. Not only that, the chance of the MPN ‘transforming’ into a different form of MPN, or acute myeloid leukaemia can be lowered.

I shall leave my ramble there;  on a positive note. Isn’t modern medicine pretty amazing?!

And also a reminder, to both myself and anyone who reads this, just because someone doesn’t look ill, doesn’t mean they are not, so always be nice.

For more info – http://www.mpnvoice.org.uk/

Further reading about drugs (the none illegal kind) –

http://www.encyclopedia.com/medicine/drugs/pharmacology/interferon

https://www.britannica.com/science/interferon

https://mpnforum.com/interferon-and-mpns/

http://brainimmune.com/the-discovery-of-interferon-the-first-cytokine-by-alick-isaacs-and-jean-lindenmann-in-1957/

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