Interferons (abbreviated IFN) are glycoproteins of the cytokine family (signalling molecules controlling the immune system). They were discovered in 1957 by Isaacs and Lindenmann, who noticed that chicken cells infected with the influenza virus produced a factor that allowed other cells to become resistant to this virus.
This factor was named interferon because it allows viral interference, the acquisition of resistance to a virus by a cell. It was later revealed that this factor was actually composed of different proteins of the same family, which were found to play various roles in the data.
IFNs are classified into 3 types: types I and III are involved in antiviral innate immunity in most cells of the body, while type II plays a major role as a communication molecule between specialised cells of the immune system.
Principles
An interferon is a natural protein made by cells in the body that has various effects on cells of the immune system. In particular, it activates macrophages (phagocytosis) and has antiviral, antiproliferative and antifibrotic properties.
Interferons inhibit cell proliferation and stimulate immune defences; certain interferons are now produced industrially and used in medicine.
The results of several studies suggest that once bound to the cell membrane, interferon triggers a complex sequence of intracellular reactions and in particular the induction of certain enzymes.
This process is believed to be responsible, at least in part, for the various cellular responses to interferon, such as inhibition of viral replication in virus-infected cells, suppression of cell proliferation, and immunomodulatory activities like increased phagocytic activity of macrophages and increased specific cytotoxicity of lymphocytes to target cells.
These activities, together or individually, could contribute to the therapeutic effects of interferon
Types of interferons
Three major classes of interferons have been identified: alpha, beta and gamma. These 3 main classes are not themselves homogeneous and can group together several different molecular species of interferon. More than 14 genetically different human alpha interferons have been identified.
Interferon alfa-2a has been shown to have many of the properties of natural human interferon alfa. It exerts its antiviral effects by inducing cellular resistance to viral infections and modulating immune system effectors to neutralise viruses or eliminate virus-infected cells.
The essential mechanism of the antitumor activity of interferon alfa-2a is not yet known. Nevertheless, a number of changes have been observed in human tumour cells treated with this substance: in HT 29 cells, a significant decrease in the synthesis of DNA (deoxyribonucleic acid), RNA (acid ribonucleic) and proteins. Interferon alfa-2a exhibits in vitro antiproliferative activity against various human tumours. It inhibits the growth of certain human tumours grafted in nude mice.
Recombinant interferon alfa-2b has demonstrated antiproliferative effects in studies using both animal and human cell culture systems and human tumour heterografts in animals. The product also showed significant immunomodulatory activity in vitro.
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral mode of action of recombinant interferon alfa-2b is not known, it appears to alter host cell metabolism. This action inhibits viral replication or, if this occurs, the daughter virions are unable to leave the cell.
Use
The discovery of the effectiveness of interferons in the antiviral fight made it possible to consider their therapeutic use. Recombinant interferon molecules are produced by bacteria, yeasts or human cells in culture in which one of the human interferon genes has been cloned: we speak of recombinant IFNs.
This method makes it possible to obtain large quantities of pure interferons that are used in medicine, for example in the treatment of some forms of cancer or viral infection.
Oncology
In oncology, interferon has a place in the treatment of certain tumours: kidney cancer, leukaemia, lymphoma, myeloma or melanoma. It is used in variable doses, according to the indications, by subcutaneous injections. In some cases, interferon can be combined with chemotherapy (skin cancers, advanced cancers of the cervix).
Interferon is likely to be the treatment of several cancers and its role as a local agent will probably expand. The list of responding cancers for alpha interferon or other subtypes as a single agent is unlikely to expand greatly over the next few years.
It is important to be aware of the possibility of both delayed and increasing extent of response with duration of treatment; adequate trials of interferon may therefore require longer periods of treatment than does conventional chemotherapy.
Viral infections
Concerning viral infections cure: treatment of isolated cells with interferon renders them resistant to infections by viruses belonging to virtually any family. Interferon induces multiple alterations in the level and state of intracellular regulatory molecules, leading to inhibition of virus replication at several possible steps.
In the case of certain DNA viruses, transcription of viral DNA seems to be inhibited. In the case of RNA viruses the target for interferon action is mainly translation. Interferon inhibits one or more initial stages of primary infection of cells by transforming or non transforming retroviruses, thereby preventing or delaying the synthesis and/or integration of viral DNA.
As with many treatments, interferons can have various side effects.
Side effects of interferon
Among the numerous side effects induced by a treatment using interferons, we can mention:
Autoimmune diseases
Interferons increase the production of certain antibodies to fight harmful substances in the body but antibodies can mistake and attack healthy cells causing low energy level, fatigue, fever, pain in the joint, urine disorder, retaining water and rash.
Mood disorders
Interferons can cause or worsen depression or mental illness and the reason for it is not known. It can cause agressive behaviour, hallucinations, mania and suicide thoughts.
Increased infections
Interferon can slow cell growth and so cause lower levels of white blood cells so that infections become more frequent or more serious causing fever or chills, sore throat, burning feeling when urinating but also body aches, flu-like symptoms and skin changes.
Stroke
Interferon can increase blood pressure and heart rate, which are both risk factors for stroke. A stroke can occur when the blood supplied to the brain is reduced or when a blood vessel in the brain leaks or bursts and damages brain tissues.
The symptoms of a stroke can include changes in speech, headache, changes in vision, confusion and weakness.
Anaemia
Interferons can slow the amount of red blood cells if antibodies attack them, these cells carry oxygen throughout the body, a lack of it can cause tiredness, weakness, pale skin, shortness of breath and irregular heart rhythm.
Risk factors
Concomitantly to the emergence of these side effects, the treatment using interferons involves contraindication for certain patients with pathologies or pre-existing conditions :
- In case of heart disease: interferons are contraindicated because they can cause arrhythmia (irregular heartbeat) and so worsen the situation and possibly cause a stroke.
- In case of cirrhosis: interferons are contraindicated because they can lower the white blood cell levels which are already down by cirrhosis and so lead to increased infections.
- In case of autoimmune diseases: interferons are contraindicated because they are caused by an overactive immune system, which interferon would only stimulate further.
- In case of severe depression or psychosis: interferons are contraindicated because interferon could make it worse because they can cause agressive behaviour, hallucinations, mania and suicide thoughts.
- In case of eye disease: interferons are contraindicated because interferons have been known to cause sight problems like blurry vision, new floaters, dark spots or empty areas in the vision.
- In case of organ transplant: interferons are contraindicated because they can cause the rejection of the organ by destroying the cells of it which can be recognized as alien and so unwanted by the organism.
- In case of pregnancy: interferons are contraindicated because they have an antiproliferative activity which can be very harmful for the foetus.
Even if interferons can be used to cure several diseases, their use includes risks. The longer the treatment, the higher and stronger the risk of side effects.
That’s why the use of this method, moreover, when mixed with other drugs, is now strictly reserved to precise cases to preserve the patient from a side effect that could be worse than the disease that was to cure at first.
