Interleukin
Interleukins (IL -x) are the cytokines scoring peptide hormones, ie they are messengers of the body's own immune system cells. The word interleukin comes from the Latin inter = between Greek and leukos = white.
Interleukins mediate communication between leukocytes, as well as other cells involved in the immune response (e.g., macrophages). They are formed by CD4 -positive T - helper cells, monocytes, macrophages and endothelial cells and act on cells of the hematopoietic system. After the order of their discovery, they are divided into several subgroups, which are indicated by numbers.
The effect of interleukins is highly variable. While IL -2 is secreted by the T cell and positive impact on the growth of these cells, IL-10 inhibits the activity of macrophages and helps reducing the defense reaction. So interleukins stimulate certain specific cells of the immune system to growth, maturation and division or prevent exactly these processes of activation.
Types
Interleukin -1
Interleukin- 1 is formed by macrophages, endothelial cells, fibroblasts and some other cells and is a pro-inflammatory signaling molecule. Endothelial cells respond to him with the incorporation of specific receptors (eg, E-selectin ) in the cell membrane. A white blood cell in the blood now binds to this receptor and can thus migrate into the damaged tissue. He displaces endothelial cells and cuts his way through the basal lamina.
The displacement and destruction of cells and connective tissue is necessary to combat pathogens and damaged or degenerated cells outside the bloodstream. In chronic inflammation, this reaction can, however, get out of control. Interleukin -1 binds to the chondrocytes and causes the release of cartilage -destroying enzymes, thus it comes to the breakdown of cartilage and ultimately to the destruction of the joints. Therapy in orthopedics is operated with an interleukin -1 antagonists since around 1998, which is obtained from the patient's own blood is injected in concentrated form and in a diseased joint. The studies conducted so far suggest a treatment option for early forms of osteoarthritis. As an inhibitor diacerein is used for example.
In schizophrenic patients were altered interleukin -1 levels in the blood, cerebrospinal fluid and in the area located in the frontal lobe ( prefrontal ) cortex are detected.
Interleukin- 1α ( IL1α )
IL1α in many cell types but predominantly produced only by monocytes and macrophages secreted. This cytokine plays an important role in the maintenance of the skin barrier function ( skin barrier function ) as well as in various immune responses. Due to its ability to increase production of Dermiskomponenten such as Collagen stimulating, it is used in the cosmetics industry.
Interleukin- 1β ( IL1β )
IL1β is produced mainly by blood monocytes and is a key chemical messenger in the response of the host organism to a number of external factors (such as lipopolysaccharides as exogenous pyrogens ). It is described in the corresponding sub- item detail.
Interleukin -2
Interleukin -2 is the most important signal to a T helper cell. After recognizing its antigen on MHC II receptor of an antigen presenting cell secretes the helper T cell interleukin-2. This signal acts mainly in an autocrine manner to herself through an intracellular signaling cascade results in activation and clonal division of T cells. Do they even recognize their antigen, they multiply, so this interleukin is one of the growth factors. In addition to the autocrine T-cell activation effect of interleukin -2 on B-lymphocytes and natural killer cells with the same effect. The production of TH2 cytokines IL-4 and IL- 5 requires IL-2.
Therapeutically interleukin -2, one of the most important interleukins.
Interleukin-3 (also multipotential CSF)
Interleukin -3 acts on the stem cells in the bone marrow and is used for stimulation of hematopoiesis after chemotherapy used after bone marrow or stem cell transplantation.
Interleukin -4
Interleukin-4 is a cytokine with anti -inflammatory properties, which among other things reduces the body's production of Th1 cells and macrophages and by IFN-gamma and IL-12. It is therefore important for the homeostasis of the immune system. IL-4 differentiate naive CD4 T- cells ( Th0 ) to Th2 cells, which in general an anti-inflammatory role is attributed. IL -4 stimulates activated B cells and leads to an immunoglobulin class switching ( class switch ) towards IgE and IgG4. The major source of IL -4 Th2 - cells themselves
Interleukin -5
IL- 5 has a positive chemotactic for eosinophils and increase the synthesis and secretion of immunoglobulin A plasma cells. It is produced by type 2 helper T cells and mast cells.
Interleukin -6
Interleukin- 6 has the effect in the liver, the increased synthesis of acute-phase proteins. We discuss both pro-and anti-inflammatory effects. It is distributed mainly of monocytes / macrophages, but also epithelial and endothelial cells ( secreted ). It has prognostic significance in the evaluation of trauma and sepsis.
Interleukin -7
Interleukin-7 is produced by stromal cells of the lymphoid organs and stimulate the growth of the precursor cells of the B and T lymphocytes.
Interleukin -8
Interleukin-8 ( IL- 8) is a CXC chemokine family, and which is produced, inter alia, by endothelial cells, monocytes, epithelial cells and fibroblasts. An important point of the chemokine are neutrophils. The main biological effects of IL-8 on granulocytes include the promotion of chemotaxis, the stimulation of the expression of adhesion molecules and activation with release of oxygen radicals, and granules, which are mediated by the chemokine receptors CXCR1 and CXCR2.
Interleukin -9
Interleukin -9 ( IL -9) is a cytokine produced by T - cells, more specifically of CD4 helper cells. IL -9 calls out many functions in lymphoid cells and mast cell lines. It is believed that this cytokine has a role in the pathogenesis of asthma.
Interleukin -10
IL- 10 acts (as well as IL- 4 and IL -11) than so-called anti- inflammatory cytokine by inhibiting the function of macrophages and thus prevents excessive inflammatory reactions. It is mainly formed of TH2 cells and regulatory T cells.
Interleukin -11
IL- 11 acts (as well as TGF- β and IL -10) than so-called anti- inflammatory cytokine by preventing excessive inflammatory responses, and thus is essential for the homeostasis of the immune system.
Interleukin -12
Interleukin -12 ( IL-12) plays a central role in the Anstoßung and continuance of a T -helper cell 1 ( TH1 ) immune response ( cellular defense ) and has influence on the course of intracellular infection. More recent research results suggest that interleukin -12 can also activate enzymes, which then are able to repair damaged genetic material quickly. Further demonstrated effect of interleukin-12 is that it promotes the ability of T- killer cells, penetrate a tumor to destroy it. IL-12 is a heterodimeric cytokine which is produced mainly by monocytes / macrophages. The production of IL -12 may be involved in the pathogenesis of autoimmunity.
Some microorganisms such as Candida albicans possess interleukin -12 inhibiting factors ..
Interleukin-13
Interleukin-13 is produced by T lymphocytes and stimulates the formation and differentiation of B - lymphocytes. Further inhibit IL-13 activation of macrophages.
Interleukin -16
Interleukin -16 is initially formed as a pro - peptide ( 80 kD ) and only then cleaved by caspase- 3 in a 14- kD monomer. The structure of the biologically active form of IL-16 corresponds to a homotetramer. IL-16, which gene is located on chromosome 15, is formed primarily by CD8 T cells. In addition, various other cell types, including mononuclear phagocytes, mast cells, eosinophils and CD4 T - cells can constitute this cytokine. For its biological effect, IL -16 binds to the CD4 glycoprotein, which thus performs the additional function of a cytokine receptor. IL -16 was identified early on as CD4 cell - specific chemotaxin. In addition, this cytokine results in native T cells to transfer from a G0 to G1 phase of the cell cycle, while promoting the surface expression of the complete IL -2 receptor, thereby to these cells as a result of exposure to IL-2 and IL-16 proliferation are stimulated. The interaction of IL -16 can with its cell-bound CD4 receptor lead to an antigen- independent cell proliferation. This fact contains in HIV-infected patients have a special meaning, since there accompanied the serum concentration of IL -16 with the severity of the infection. IL- 16 also plays a role in disease Crohn's disease, multiple sclerosis, and autoimmune thyroiditis.
Interleukin -17
Interleukin-17 is a newly described Signalzytokin of Th17 cell type that is associated with a variety of autoimmune diseases in murine models. Other cytokines of this cell type are IL-21 and IL- 22nd IL -17 appears to be involved in mediating the inflammatory fibroblasts. He is also said to have a role in neutrophil recruitment.
Interleukin -18
Interleukin -18 is a cytokine that belongs to the IL-1 cytokine receptor superfamily, has functional similarities with IL- 12 and has an important role as a regulator of natural and acquired immunity. Made from a 24 - kD precursor peptide, IL- 18 (analogous to IL- 1β ) by interleukin -1 converting enzyme protease ( also called caspase -1) is split into its bioactive 18- kD form. IL- 18 is formed by various hematopoietic and non- hematopoietic cells, including macrophages, dendritic cells, Kupffer cells, keratinocytes, osteoblasts, intestinal epithelial cells, microglia cells, fibroblasts and cells of the adrenal cortex are. The specific for the cytokine receptor complex, IL - 18R, corresponds to a heterodimer consisting of a ligand-binding α - chain and a signal transducing β chain. IL- 18R is expressed primarily on macrophages, neutrophils, NK cells, endothelial cells, smooth muscle.
IL -18 was detected in patients with rheumatoid arthritis in increased concentration in the joint lining ( synovium ).
Interleukin-21
Interleukin 21 is a cytokine with important regulatory effects on cells of the immune system, including natural killer cells (NK - cells) and cytotoxic T- cells infected with a virus, or can destroy cancer cells. It also plays a role in Hodgkin's lymphomas.
Interleukin -22
Patients suffering from psoriasis ( psoriasis) patients produce enhanced the cytokine interleukin- 22nd The more of these in the skin, the more pronounced the disease. Tests on mice show that IL -22 blockade attenuates inflammation and abnormal skin growth diminishes. In contrast, IL22 injections solve in healthy animals from Psoriasis -like symptoms.
Interleukin -23
In many autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, psoriasis and Crohn's disease can interleukin -23 stimulate the production of T- cells, which are then directed against one's own body. Moreover, it may interfere with the indirect tumor destructive effect of interleukin-12.
Interleukin -31
Interleukin -31 is formed by lymphocytes. IL -31 receptors have been found on neuronal cells in dorsal root ganglia, the itching (pruritus ) them. It would be a potential pharmacological target ( IL -31 antagonists) with many associated with itching diseases ( atopy, cholestasis, uremia ). It is controversial whether histamine in the pathogenesis of pruritus plays a role.
Use as a therapeutic agent
In an immunotherapy or immunomodulation with interleukin, such as IL -2 in cancer immunotherapy against metastatisierenden renal cell carcinoma, is trying to encourage the defense of an organism. Malignant tumors or an infection, such as HIV, is to be met by the administration with the body's own funds.
Most in the treatment of malignant tumors ( renal cell carcinoma, malignant melanoma) combined preparations of interleukin and other means are used, such as interferon and / or cytostatics. The side effects of treatment with interleukin -2 are considerable: for example, fever, fatigue, rashes, palpitations, edema.
Today are frequently and successfully applied so-called "anti- interleukins " in Crohn's disease and especially in autoimmune- related rheumatic diseases.