Interferons are proteins (molecules, substances) produced naturally by cells in response to a large variety of stimuli. They were discovered in 1957 by two researchers, Isaacs and Lindenman, in the course of their studies on the infection of laboratory-grown tissues by the influenza virus. The two scientists isolated an interfering factor from these crops - hence the name interferon - with the growth of the virus.
Later it was discovered that interferons, in addition to the ability to confer resistance to many viruses, have the ability to inhibit the growth of normal and malignant (tumor) cells and to modulate the functions of various cells of the organism's defense system (system From these multiple functions derive the different therapeutic applications of interferons, ranging from viral infections (hepatitis B and C) to tumors and autoimmune diseases.
Mechanism of action
Interferons are part of a large family of proteins called cytokines, name composed of the root I quote- cell e kinetic / kinetic (from the Greek κινέω "to move, to set in motion").
They are, therefore, molecules that spreading in the tissues / organs in which they are produced, or in which they are transported by the bloodstream, allow communication between cells at a distance.
Interferons act on cells by binding to molecules present on the cell surface, the so-called receptors, that trigger a series of reactions. They culminate in the production of numerous proteins (called interferon responsive proteins) which, in turn, play various roles in the defense of the cell from infectious or, in any case, dangerous agents.Types of Interferons
Types of Interferons
Three classes of interferons have been identified. They differ from each other in the sequence of amino acids (amino acids are the "bricks"That make up proteins), for the cells from which they are produced, for the receptor on target cells and for functions. They include:
- type I interferons, also called alpha / beta (a / b), constitute the most numerous class, 13 subtypes of interferons alpha (IFN-α), interferon beta (IFN-b), and the interferons epsilon, kappa, and omega belong. The most studied interferons, also for their clinical application, are IFN-α2 and IFN-b. Type I interferons can be produced by all cell types and possess antiviral activity, the ability to regulate immune system functions, and the ability to regulate cell growth and differentiation (i.e., the ability of cells to acquire specialized functions based on to the fabric they are part of)
- type II interferon or gamma interferon (γ), the only member of this class is interferon gamma (IFN-γ) produced by the cells of the immune system. It acts on them with multiple functions, mainly activating them to fight infections and tumors
- type III interferons or lambda interferons (λ), more recently identified (about 15 years ago) lambda interferons (IFN-λ1, IFN-λ2, IFN-λ3, also known as IL29, IL28A and IL28B) have functions similar to type I IFNs, although their sequence of amino acids and the cell receptors they bind to are different. No members of this class are currently approved for clinical use.
Clinical Use of Interferons
A subtype of alpha interferon, IFN-α2, was the first interferon approved for clinical use in the treatment of hairy cell leukemia, in 1986. Since then, several other therapeutic indications have been added. According to the provisions of the AIFA, in Italy, interferon can be prescribed in the following viral and tumor diseases:
- chronic hepatitis B and hepatitis C
- hairy cell leukemia, chronic myeloid leukemia, Kaposi's sarcoma related to AIDS or other conditions that reduce the function of the immune system (immunosuppression), follicular non-Hodgkin's lymphoma, malignant melanoma, advanced renal cell carcinoma, cutaneous T-cell lymphoma, myeloma multiple, carcinoid tumor, warts
It should be noted that the new generation antivirals that act directly on the virus are replacing interferons in the treatment of hepatitis C virus (HCV) infection. These new drugs, in fact, are well tolerated, induce a strong response in a short time and promise to lead to the elimination of the disease.
More targeted therapies are progressively replacing interferon alpha in the treatment of some cancers (advanced renal cell carcinoma, melanoma, multiple myeloma and advanced follicular lymphoma).
Another subtype of type I interferon, IFN-b, is used for therapy of the form relapsing-remitting of multiple sclerosis. Interferon does not cure multiple sclerosis, but it can decrease the frequency and severity of episodes. Approved in 1994, IFN-b was the first drug available for multiple sclerosis and remains one of the first-line therapies today. for this disease.
To date, IFN-γ has been approved for the treatment of chronic granulomatous disease. In particular, to reduce the frequency and severity of severe infections caused by the disease. It is also used to slow the progression of malignant osteopetrosis.
Formulations and methods of administration
Interferons are available only with a doctor's prescription and are administered by intramuscular or subcutaneous injection with the exception of their use in condylomatosis which occurs directly inside the lesion. Depending on the type of molecule and the pharmaceutical company that produces it, the " Interferon is contained in ready-to-use self-injecting pens, pre-filled syringes or injection vials.
Among the different chemical formulations existing, the most used are recombinant interferon (ie produced in the laboratory) and pegylated interferon. The pegylated interferons are molecules modified through the "insertion of a polyethylene glycol (PEG) chain which allows to lengthen the"half-life (increase stability). This allows for a single weekly administration of the drug instead of the multiple injections required if non-pegylated interferon is used.Side Effects of Interferons
Side Effects of Interferons
The most common reaction to the use of interferon is a set of flu-like symptoms (symptoms): fever, chills, body aches and headaches. They are very common but generally disappear spontaneously after the start of therapy. In some cases, however, they can induce a major debilitating state.
One of the most serious - although less frequent - problems is neurological toxicity which is manifested by the onset of depression and suicidal ideas, disorders that must be recognized and treated quickly and which have been observed both in adults (about one third of patients with interferon alpha) and in children.
Long-term side effects include fatigue, weight loss, and autoimmune disorders (including thyroid dysfunction, diabetes, and dermatological complications).Bibliography
Mayo Clinic. Drugs and Supplements (English)
Antonelli G, Scagnolari C, Moschella F, Proietti E. Twenty-five years of type I interferon-based treatment: A critical analysis of its therapeutic use. [Synthesis]Cytokine & Growth Factor Reviews. 2015; 26: 121-131
Paul F, Pellegrini S, Uzé G. IFNA2: The prototypic human alpha interferon. Gene. 2015; 567: 132-137