Interferons are tissue hormones composed of relatively short-chain polypeptides, proteins, or glycoproteins. Together with interleukins and other groups of substances, they belong to the cytokines that initiate and control the immune responses of the immune system. Interferons are produced mainly by cells of the immune system, but also by fibroblasts, and primarily control antiviral and antitumor immune responses.
What are interferons?
Interferons (IFNs) are endogenous tissue hormones composed of short-chain polypeptides, proteins, and glycoproteins of up to 166 amino acids. Due to their properties and effects in human metabolism, they are classified as cytokines together with interleukins, which have comparable properties and effects, and with other substance groups. Cytokines initiate and control immune responses of the immune system and thus perform vital tasks. Interferons can be divided into the three classes IFN-Alpha, also called leukocyte IFN, IFN-Beta and IFN-Gamma. While most of the 23 known IFN-alpha variants are proteins of 166 amino acids each, beta and gamma IFNs are predominantly glycoproteins also of 166 amino acids, or 144 amino acids in the case of gamma IFNs. Interferons are important for recognizing and fighting viruses and cancerous tumors. Interferons stimulate and control complex immune responses in specialized cells of the immune system or directly in tissue cells attacked by viruses or other pathogens or in degenerated tumor cells. Interferons do not need to penetrate target cells to stimulate and “distribute their messages,” but merely dock at specific receptors.
Function, effects, and roles
In concert with interleukins, colony-stimulating factors, tumor necrosis factors, and chemokines, which together constitute the class of cytokines, interferons very substantially initiate and control immune responses to cells attacked by viruses or other pathogenic agents. The same is true for cells that have been identified as tumoral. In terms of their mode of action, interferons are comparable to interleukins, although a certain specialization in virus attack and in tumor tissue can be identified in the case of interferons. For humans, the body’s own fight against viruses and cancer is of high – and sometimes vital – importance. The immune response that interferons provide is very complex. Interestingly, interferons do not usually combat invading viruses directly, but rather dock onto specific receptors in the cells and cause them to produce certain proteins (enzymes) with antiviral activity, which help infected cells to impair the virus via certain metabolic processes or even render it harmless. This process can also take place in neighboring, non-infected cells, so that these can protect themselves from infection. Alf- and beta-IFN provide the cells with guided help to help themselves with their activities. Gamma interferons, as a tissue hormone, are particularly specialized in activating and supporting macrophages.
Formation, occurrence, properties, and optimal levels
Alpha interferons are secreted not only by immune cells but also by many other tissue cells, especially cells infected with viruses or bacteria. IFN-alpha stimulates infected and neighboring cells to produce certain protein-degrading enzymes to degrade viral RNA and prevent viruses from replicating their RNA. Bacterial membranes can also be partially dissolved or entire bacteria can be rendered harmless and transported away by phagocytes. Beta-interferons, also known as fibroblast interferons, are secreted primarily by fibroblasts located in the extracellular space and infected with viruses. Properties and actions of IFN-beta are very similar to those of IFN-alpha. They can even dock to some of the IFN-alpha receptors. The properties of gamma interferons differ from those of IFN-alpha and IFN-beta. IFN-gamma is secreted predominantly by TH1 cells, which are part of the adaptive immune system. Gamma interferon is produced whenever there is contact with antigen-presenting macrophages. For example, this is always the case with bacteria phagocytizing macrophages.In addition to antiviral and antitumor properties, IFN-gamma also have immunomodulatory effects because they support the adaptive cells of the immune system that have adapted and adjusted to fight current pathogens.
Diseases and disorders
Interferons, in concert with interleukins and other cytokines, initiate and control immune system reactions called immune responses. Some of these are extremely complex processes with many players involved. It is therefore likely that individual steps of the immune response may be disturbed or that the immune system as a whole reacts too weakly or too strongly. Disturbances in either direction can lead to mild to severe symptoms and disease. Since most interferons also cross the blood–brain barrier, disturbances in the release of interferons can also have considerable psychological effects and – in the case of weakening – their protective function in the CNS can no longer be performed or only to a limited extent. On the other hand, artificially supplied interferons are also used for therapeutic purposes, such as in multiple sclerosis (MS) and hepatitis C and B. Symptoms similar to those of a disorder of interferon production can occur if only the functionality of the receptors on the cell membranes is disturbed. Several genetic defects are known that lead to dysfunction of certain receptors and cause corresponding symptoms of deficiency. Interferons then cannot dock or “find cells” to which they would have to attach in order to perform their tasks. In certain chronic viral diseases (Epstein Barr Virus, Zoster, Herpes, Borrelia and others) a disturbed balance between interferon and interleukin secreting Th1 and Th2 cells already has an effect. Similar observations have been made in HIV infections. Thus, the homeostasis between the different cytokines is of high importance. Regarding possible systemic overproduction of interferons not caused by local inflammation, so-called “gain mutations” have been reported. The mutations lead to altered – usually massively expanded – secretion of certain interferons, which can be life-threatening.
