Interleukins form a subset of cytokines, cellular messengers that control the immune system. Interleukins are short-chain peptide hormones of 75 to 125 amino acids. They mainly control the local deployment of leukocytes at sites of inflammation, although they can also have systemic effects as in triggering fever.
What are interleukins?
Interleukins (IL) are short-chain peptide hormones of 75 to 125 amino acids. They form one of several subclasses of cytokines that control the immune response. As messengers, interleukins have a similar spectrum of use as interferons, which also form a subclass of cytokines. However, interleukins are particularly specialized in the control of leukocytes. Some interleukins also exhibit systemic effects, for example, by being able to induce fever, whereas interferons are more specialized for defense against viruses and have antitumor capabilities. Unlike neurotransmitters, interleukins and interferons are specialized in communicating with cells of the immune system with each other and with tissue cells. Their main action usually takes place locally in tissues. To communicate with cells of the immune system or with tissue cells, interleukins do not need to enter the cells; they simply dock onto specific receptors of the cells, which is sufficient to cause the immune cells to proliferate, differentiate, and become active.
Function, action, and roles
Of the more than 40 different interleukins, each performs a specific task. Overall, interleukins control the deployment of leukocytes, and to some extent also the deployment of T helper cells, monocytes, and macrophages, as well as other immune cells. The basic tasks are to stimulate cells of the immune system to mature, grow and divide, i.e. to multiply, when required. This also includes the opposite process, the abrogation of certain immune responses. Interleukin-1 has the ability to produce fever, when certain conditions occur. IL-1, together with IL-6 and tumor necrosis factor, is therefore one of the so-called pyrogens. IL-2 is specialized in stimulation, proliferation and differentiation of T helper cells, B cells and natural killer cells. The most important task of IL-3 is the emission of stimulation stimuli that cause certain pluripotent stem cells to mature into erythrocytes, granulocytes or other cells of the immune system. IL-4 also has the ability to transmit proliferation and differentiation stimuli to T cells, but at the same time it has an inhibitory effect on macrophage activity. IL-4 thus also has an anti-inflammatory effect. Target cells of certain interleukins can be stromal cells or fibroblasts as in the case of IL-17, in addition to all cell types belonging to the immune system. For modulation of inflammatory processes in the skin, interleukin-20 probably directly controls the immune response of keratinocytes in the uppermost layer of the skin. A few interleukins such as IL-28 and IL-29 recognize cell lines infected by viruses. IL-24 is probably the only interleukin that can recognize tumor cells and exert an antitumor effect by inhibiting growth and inducing cell apoptosis, self-induced cell death.
Formation, occurrence, properties, and optimal levels
Most interleukins are secreted by cells of immunologic relevance predominantly into the intercellular domain, where they can dock to the secreting cell itself or to other cells of the immune system. Only in a few exceptional cases do specialized interleukins occupy receptors of cells that do not belong to the immune system. One exception, for example, is IL-33, which is released in the lungs and skin, can dock to receptors of the IL-1 family. As with IL-4, IL-5 and IL-13, the target cells are mostly T cells and to some extent also eosinophils and mast cells. In principle, interleukins focus on communication between cells. It is mostly a small-scale, locally acting communication, although in exceptional cases systemic effects are also achieved. Some interleukins resemble growth factors because their influence on T cells, monocytes and lymphocytes is comparable to that of growth factors. Due to the high dynamics resulting from the changing demands on the immune system, the specification of a reference value or an optimal value for their occurrence in the body is not meaningful.However, problems can arise from reduced or excessive secretion, such as that observed in allergic reactions.
Diseases and disorders
The very complex interaction of the individual components of the immune system causes a variety of possible disorders, weakening of the immune response, or an excessive reaction to certain challenges, which can lead to mild to severe symptoms of disease. In some cases, however, it is not the secretion of cytokines that is disturbed, but rather the problem lies with impaired receptors to which interleukins and other cytokines cannot dock. The immune response in tissue inflammation is dominated by IL-1. As a pro-inflammatory signaling substance, its activity can be pathologically increased so that not only dead body tissue is phagocytized and removed, but also healthy cells are attacked, causing diseases such as rheumatism and osteoarthritis in joints. In these cases, an antagonist to IL-1 can help by curbing the immune response by IL-1. Antagonists to IL-1 may also be used in other autoimmune diseases such as Crohn’s disease, MS, and psoriasis. Because interleukins consist of relatively short-chain proteins or polypeptides, most of them can also cross the blood–brain barrier. In some cases, specialized astrocytes perform the transport. Although there is no direct specificity of the individual interleukins with respect to schizophrenia and depression, clear correlations can be found, for example, between hypersecretion of IL-2 in schizophrenia and of IL-6 in depression. Interleukins and other cytokines exert strong influence on neurotransmitters such as dopamine, serotonin, epinephrine, norepinephrine, and others.
