Interleukin, commonly abbreviated as IL, is the umbrella name for a group of several natural proteins that play an important role in the human body. They allow cells to communicate between them, controlling their development, expansion and features. They were found to be very important in immune responses such as inflammation.
The molecules that facilitate messaging between cells are collectively known as cytokines. Interleukins are a part of this group and can influence cellular reactions. None of the cytokines are actually present inside the cells. The body reacts and produces them rapidly in the presence of pathogens or as a reaction to another strong stimulus. Receptor molecules are present on the surface of cells and interleukins quickly move to their target and bind on it. Depending on the cell and the protein, this reaction triggers a series of signals as part of the body's response.
The name of these proteins comes from the combination of two words, inter (which means communication) and leukin, which indicates that leukocytes usually produce them. Today, scientists know that other body cells can produce interleukins, besides leukocytes. However, the name has stuck, even if it is not entirely correct. Dr. Vern Paetkau from the University of Victoria is credited for the term.
Cytokines produced by lymphocytes that have the ability to alter immune responses are known as lymphokines. Due to their effects, some interleukins are included in this group.
The body produces the natural proteins named interleukins in order to make the immune system more effective against threats. As soon as an infection or another external threat is detected, interleukins are produced as a response. Many varieties exist and only a part of them have been identified and researched, while the function of many others remains obscure. Interleukins can start a variety of immune responses as a reaction against pathogens. Common examples include inflammation, allergic reactions, cell regeneration, pain or fever.
Interleukins and other signalling molecules part of the cytokine family are very important for the human immune system. However, they do not initiate the actual response. These proteins only serve as messengers between cells and are especially used to activate white blood cells and let them know there is a threat. The various cells will then react to the message.
Since interleukins are known for their role in immunity, scientists have investigated their use in the treatment of very serious conditions such as rheumatoid arthritis, Crohn’s disease or cancer. The amount of interleukins produced by the body is quite limited, so researchers have tried to produce them in labs. After a method was discovered, these proteins are now available for testing. Clinical trials have established that a high dose of interleukins can make white cells twice as effective in the fight against pathogens or tumour cells. A special form of biological therapy based on interleukins has also been developed in order to help people recover after very aggressive cancer treatments that destroy tumours but leave the body very weakened.
The treatments with interleukin also have known side effects. These include chills, fever, nausea, vomiting and swelling. Interleukins can severely reduce blood pressure and increase the risk of bleeding and bruising. These side effects can be severe enough to require hospitalization. However, most of them have a short duration and disappear soon after the treatment ends.
Another concern related to interleukin therapy is the risk of having a hyperactive immune system. While a strong immune response has obvious benefits, it can also be very dangerous and trigger autoimmune diseases that can't be cured, like multiple sclerosis, lupus or fibromyalgia. These conditions are very poorly understood but the cause seems to be the lack of communication between cells. Interleukins are also required to send a very important signal to the T suppressor cells that are part of the immune system. These cells then relay the signal that the fight against infection is over and the white cells must stand down. If the cells fail to get this message, they continue to attack healthy cells and the autoimmune disease starts. This is either caused by faulty T-cells or by white cells ignoring their message for some unknown reason.
Interleukins have been identified for the first time in the 1970s but their role wasn't well understood. Scientists gave them the current name because they assumed that interleukins were produced by leukocytes in order to communicate with other white blood cells. This explains the name, which means "communication between leukocytes". They also assumed that interleukins only play a single role, influencing the response of the immune system. This is indeed their most important role but today we know that these proteins have many other functions in the body. They can also be produced by several types of cells and interact with many others, including many types that are not part of the immune system at all. Interleukins are a lot more important to the body than it was initially thought.
In total, 17 types of interleukins have been discovered so far. They have been named in order, starting with IL-1 and ending with IL-17. All of them have a role in the immune system, but only some of these functions are well understood. The white blood cells responsible for the so-called acquired immune response, the T and B lymphocytes, are activated by interleukins IL-1 and IL-2. IL-2 also boosts the growth and multiplication of these types of lymphocytes. Inflammation is triggered by IL-1, working with IL-6. B lymphocytes release more antibodies when activated by IL-4, while the production of natural killer cells and cytotoxic T cells is increased by IL-12. The presence of certain pathogens triggers the release of a number of interleukins in response, which control the intensity of the immune response and can determine the progression of the disease.
Interleukin 1 alpha (IL1 alpha) and interleukin 1 beta (IL1 beta) are two very important cytokines that are involved not only in immune responses but also hematopoiesis and inflammation. Two varieties of IL-1 receptors have been identified in both humans and mice. They have different pharmacological characteristics, limited sequence similarity (28%) and have three extracellular immunoglobulin domains. These are named the type I and type II receptors and scientists have been able to clone them. Soluble and transmembrane forms exist for both of these receptors. It is possible that the extracellular portion of the membrane receptors creates the soluble type of the IL-1 receptor.
IL-1 also appears to be very important for the human central nervous system. The type I IL-1 receptor has been genetically removed from some mice, which were found to have severe memory problems, especially the part that depends on the hippocampus. The part of memory that doesn't depend on this region of the brain was not affected. Scientists have injected wild-type neural precursor cells into the hippocampus of these mice, the cells later transformed into astrocytes, which are a type of cell with interleukin-1 receptors. Afterwards, the hippocampal-dependent memory of the animals was restored, and the long-term function returned to a level close to normal.
The production of T cells and some of the B cells is controlled by T lymphocytes through the release of some special proteins, one of which is interleukin 2 (IL2). These are produced by T-cells after stimulation from either antigen or lectin and have various functions in the immune system. The release of the lymphokine IL2 triggers an increased number of T cells. It also binds to the specific receptors found on certain B cells, stimulating them to grow and to synthetize more antibodies. It needs the cleavage of a signal sequence for activation and is formed as a single glycosylated polypeptide.
Interleukin 3 (IL3) is another important cytokine. It influences macrophages and granulocytes, supervising their production and activity. In vivo, the protein is found as a monomer. The cleavage of an N-terminal signal sequence triggers the production of IL3, which is handled by both T cells and mast cells after activation.
T lymphocytes and T-cell lymphomas can be stimulated by chemical activators such as phorbol esters, as well as antigens or mitogens, in order to produce IL3. The myelomonocytic leukaemia cell line WEHI-3B also plays a vital role in its formation. Leukemia seems to develop after genetic damage to this cell line that is responsible for the production of the interleukin IL3.
CD4+ T cells produce interleukin 4 (IL4), which is designed to increase the multiplication of B cells. It is also involved in somatic hypermutation and the class switch recombination of these cells. The release of IL4 also increases the role of Th2 cells in the class switch recombination to the IgG1 and IgE isotypes and other function of B cells.
Interleukin 5 (IL5) is a cytokine specific for the lineage for eosinophilpoiesis. It is also known as EDF, or the eosinophil differentiation factor. As the alternative name implies, it handles the growth and activation of eosinophil. As a result, it is linked to diseases such as asthma, which involve higher levels of this compound.
Several types of white blood cells, such as specialized T cells, macrophages and endothelial cells, produce interleukin 6 (IL6) as a response to traumas or tissue damage. This compound is considered to be both an interleukin and a cytokine, which means that it has a double role as a signalling molecule and a signalling protein. This makes it an extremely important messenger that sends information between body cells. Its role depends on the local conditions, for example IL6 can trigger inflammation but also signal the end of such a reaction. Besides the quantity produced naturally inside the body, interleukin-6 can also be manufactured in labs.
The release of interleukin 6 starts the so-called acute-phase reaction of the immune system, by stimulating it. In this phase, a large number of compounds with a large spectrum generic antibody reaction are produced, named acute-phase proteins. The most important part of this process, triggered by c-reactive proteins, is phagocytosis. It is a very effective defensive mechanism that destroys pathogens by surrounding them with cells. The acute-phase reaction has side effects such as fever. The temperature increases because more energy is diverted to muscular and fat tissues during the acute-phase reaction.
Interleukin 6 can also be classified as one of the myokines. These are special cytokines that are released into the blood after muscular contractions. They start multiple biological processes inside the body, one of which is the assimilation of fats. The breakdown and use of glucose is also increased, due to superior resistance to insulin. Due to these effects, IL6 is investigated as a possible treatment for type II diabetes, obesity and other metabolic disorders.
A balanced level of interleukin 6 is needed for optimal health. While it is beneficial for immune system support, too much of it can be harmful. An excessive amount of interleukin-6 leads to defective immune responses and can trigger serious autoimmune conditions, which are usually impossible to cure. Very high levels of interleukin-6 have been detected for example in the synovial tissue of people who suffer from rheumatoid arthritis. One of the treatments considered as a treatment for this disease involves preventing the binding of interleukin-6, by developing an antibody against the receptor for this protein.
Early lymphoid cells of types B and T are stimulated to grow by the release of the cytokine interleukin 7 (IL-7). It seems to have a connection with another compound, known as interleukin 9 (IL-9). IL-9 is also involved in the development of helper T-cells, independent of the action of IL-2 and IL-4.
Some body cells, like epithelial cells, macrophages, airway smooth muscle cells and endothelial cells, produce the chemokine interleukin 8 (IL-8), IL-8 is a precursor peptide of no less than 99 different varieties of amino acids. The process of cleavage then transforms it into isoforms with active IL-8 action.
The protein interleukin 10 (IL-10) has a suppression role and prevents activated macrophages and helper T cells from producing some types of cytokines. It is structured as four conserved cysteines in the form of disulphide bonds and it is found in the composition of more than 160 amino acids. The BCRF1 protein of the Human herpesvirus 4 (Epstein-Barr virus) has a highly similar structure to IL-10, as well as the protein E7 of Equid herpesvirus 2 (Equine herpesvirus 2). It reduces the release of gamma-interferon.
Interleukin 11 (IL-11) is a protein that causes the production of more platelets by boosting the process of megakaryocytopoiesis. It also activates osteoclasts, with multiple effects, such as the reduction of macrophage mediator production and the inhibition of epithelial cell proliferation and apoptosis. The release of this protein can have an important protective role on the hematopoietic, osseous and mucosal mediation.
Interleukin 12 (IL-12) is a heterodimer that bonds to disulphide and plays a critical role in the protection of cells. It increases resistance against the Measles virus, Human immunodeficiency virus 1 (HIV), Leishmania, Toxoplasma and other intracellular germs. IL-12 stimulates the Th1 cellular immune responses in general and boosts the cytotoxic function of NK cells. The role of this reaction against inflammatory bowel disease and multiple sclerosis is greatly enhanced. Scientists suspect that these diseases could be treated by suppressing the effect of IL-12. However, conditions that trigger pathological Th2 responses might be treated with an increased dosage of recombinant IL-12.
Interleukin 13 (IL-13) is considered potentially important in starting and controlling immune and inflammatory reactions. It is classified as a pleiotropic cytokine that reduces the synthesis of other inflammatory cytokines. It also balances the production of interferon-gamma, alongside IL-2.
Interleukin 15 (IL-15) is another cytokine with a large action spectrum. It activates certain cell immune responses but also plays many other biological functions. It interacts with some parts of IL-2R, such as IL-2R beta and IL-2R gamma, in order to boost the production of T lymphocytes as part of a defensive mechanism.
Many cells, such as lymphocytes and a part of the epithelial cells, release the protein designated as Interleukin 16 (IL-16). This pleiotropic cytokine also plays several roles. It filters the activation of T cells, prevents the replication of viruses like HIV and attracts chemicals.
Researchers have also discovered that various cells that are part of the CD4 molecule are attracted and activated by IL-16. Such examples include dendritic cells, monocytes and eosinophils. Fully developed IL-6 compounds use CD4 as their cell signalling receptor.
When they are activated, memory T cells release the Interleukin 17 (IL-17) cytokine in order to start a strong inflammatory reaction. The entire mechanism of IL-17 appears to be very old, an ancient system of signals that has been preserved during the evolution of vertebrates.