What are interleukins?
Interleukins are a kind of large group of cytokine protein molecules that play a vital role in stimulating an immune response to a pathogenic antigen. They also help in regulating cell growth, differentiation, proliferation, maturation, activation and motility of immune cells.
Discovery and definition of Interleukin
Interleukins were discovered in the year 1970. Initially, it was thought that interleukins were produced by leukocytes(white blood cells), and as such, these molecules were named interleukins, which defines the meaning of the word as “between leukocytes”. But through later observations, it was found out that interleukins were also produced by various cells of the body.
Interleukin production
Production
- Interleukin production is a transitory process. Most of the interleukins are encoded by an unstable mRNA(messenger RNA) which results in an ephemeral synthesis of these molecules. Once synthesized, these molecules are briskly released.
- These interleukins then migrate to a particular target cell with the aid of a receptor molecule that binds to the surface of that cell.
- As a result, a cascade of signals is set off within the target cell that eventually transmutes the action of the target cell.
- Oftentimes, interleukins have a great impact on the synthesis and activation of other interleukins. For example, the lymphocytic activation promoted by IL-1 influences the release of IL-2.
Interleukin in humans and its function
Interleukins observed in human diseases are:
To induce fever, IL-1 acts as an endogenous pyrogen and stimulates the hypothalamus.
- T-cell hyperactivation and T cell-mediated autoimmune responses are induced when IL-2 is experimentally inhibited.
- IL-2 is also used in the immunotherapy of melanoma and renal carcinoma.
Inhibition of IL-10 hyper activates the macrophages which leads to the development of an inflammatory bowel disease.
Through its anti-inflammatory effects, IL-27 isknown to suppress autoimmune reactions.
IL-29 is used as a biomarker of joint inflammation in patients with osteoarthritis.
Increased levels of IL-36 can be seen in human psoriasis.
Different types of interleukin and its functions
- Interleukins are known to exhibit both autocrine and paracrine functions. These molecules are used in animal studies to carry out systemic inquiry pertaining to clinical medicine.
- First interleukin, interleukin-1(IL-1) was discovered in 1977. As many as 40 ILs(Interleukins) are known today. Each IL shows distinct cellular function and its production may not be confined to only one kind of cell.
Interleukin-1 (IL-1)
- IL-1 is secreted by macrophages, B cells, astrocytes, endothelium, fibroblasts and granular lymphocytes.
- It activates lymphocytes and stimulates macrophages, thereby increasing the release of hepatic acute-phase proteins(APPs).
- Apoptosis can also be seen in many cells.
Interleukin-2(IL-2)
- IL-2 is synthesized by T-cells. It mainly affects the;
- Proliferation and differentiation of T cells,
- The proliferation of B cells, and
- Proliferation and activation of NK cells (natural killer cells).
- Increases the synthesis of cytokines, causes Fas-mediated apoptosis and promotes the regulatory development of T cells.
- Interleukin-2 is also responsible for the activation of cytotoxic lymphocytes and macrophages.
Interleukin-3(IL-3)
- IL-3 is produced by T cells and stem cells. It functions as a multilineage colony-stimulating factor.
- It mainly regulates the concentrations of different types of blood cells.
- Also plays a role in inducing the proliferation and differentiation of committed progenitors and early pluripotent stem cells.
Interleukin-4(IL-4)
- IL-4 is predominantly made by mast cells, Th2 cells, eosinophils, basophils, neutrophils and a subgroup of activated T cells.
- It helps in monitoring the production of antibodies, inflammation and hematopoiesis.
Interleukin-4 (IL-4) bound to its receptor cell on the membrane of a cell.
3. IL-4 governs the development of responses in effector T cells.
4. It is also responsible for the inhibition of IFN activation on macrophages mediated by gamma cells which ultimately results in the killing of intracellular pathogens.
Interleukin-5(IL-5)
- IL-5 is secreted by Th2 cells, eosinophils and mast cells.
- It functions in the chemotaxis of eosinophilic cells.
Interleukin-5 (IL-5) increases the synthesis of immunoglobulins.
- It greatly helps in promoting the differentiation and survival of these cells.
Interleukin-6(IL-6)
- IL-6 is made by macrophages, T and B cells and fibroblasts.
- It functions as a stimulator of acute-phase proteins and influences their responses.
- Also helps in the differentiation of B-cells.
Interleukin-7(IL-7)
- IL-7 is synthesized by stromal cells of bone marrow.
- It acts on T-cells and the lymphoid cells of the bone marrow.
- Is responsible for the proliferation of T cells as well.
Interleukin-8 (IL-8)
- IL-8 is released by fibroblast cells and monocytes–a type of leukocyte(white blood cell).
- It is responsible for inducing neutrophil chemotaxis, releasing granules and superoxides.
- And helps in the process of angiogenesis; a process that requires the migration, growth and differentiation of endothelial cells lining the blood vessels for the purpose of forming new blood vessels
Interleukin-9(IL-9)
- IL-9 is majorly produced by Th2 cells, Th9 and Th17 cells, regulatory T-cells, mast cells and NKT cells.
- Helps in preventing apoptosis of T-cells, thereby stimulating its proliferation.
- Plays a role in the activation of mast cells and enhances the process of erythropoiesis.
Interleukin-10 (IL-10)
- IL-10 is secreted by Th2 cells.
- It acts as an inhibitor of IL-2, IL-12 and gamma IFN.
- It is responsible for decreasing the antigen presentation, co-stimulatory molecules and the MHC class II expression of dendritic cells on macrophages.
- Also suppresses the responses of infectious Th17 cells.
Interleukin-11 (IL-11)
- IL-11 is synthesized by stromal cells of bone marrow and fibroblast cells.
- It mainly affects the formation of osteoclast cells that participate in the resorption of aged bones.
- It also plays a role in raising the platelet count in vivo and hinders the production of pro-inflammatory cytokines.
Interleukin-12 (IL-12)
- IL-12 is secreted by monocytes.
- It induces Th1 cells and the production of IFN gamma by T-cells and natural killer cells(NK cells).
Interleukin-13 (IL-13)
- IL-13 is produced by Th2 cells, mast cells and NKT cells.
- It increases epithelial cells mucus production and synthesis of collagen by fibroblast cells.
- IL-13 is produced by Th2 cells, mast cells and NKT cells.
- It increases epithelial cells mucus production and synthesis of collagen by fibroblast cells.
Interleukin-13 (IL-13) regulates the production of IgE molecules.
Interleukin-14(IL-14)
- IL-14 is released by T-cells.
- It stimulates the proliferation of activated B-cells and also inhibits the secretion of immunoglobulin.
Interleukin-15(IL-15)
- IL-15 is made by muscles, epithelial cells and monocytes.
- It regulated the proliferation of B-cells and T-cells, NK cell memory and cytotoxic T lymphocytes(CTLs).
Interleukin-16(IL-16)
- IL-16 is synthesized by cytotoxic T lymphocytes(CTLs) and eosinophilic cells.
- It influences the chemotaxis of T-cells.
Interleukin-17(IL-17)
- IL-17 is secreted by Th17.
- It triggers the release of IL-6 and various pro-inflammatory cytokines.
- It is also responsible for emphasizing antigen presentation activities and in stimulating chemokines by endothelial cells.
Interleukin-18(IL-18)
- IL-18 is mainly produced by macrophages, liver cells and cells that synthesize keratin.
- It greatly influences the activity of NK cells and regulates the production of IFN gamma.
Interleukin-19(IL-19)
- IL-19 is made by Th2 cells.
- It acts on immune cells and also plays a role in triggering the resident vascular cells as well.
Interleukin-20(IL-20)
- IL-20 is synthesized by activated epithelial cells and immune cells.
- It also acts as a regulator of intercellular signalling between the epithelial cells and immune cells at the site of inflammation.
Interleukin-21(IL-21)
- IL-21 is made by CD4 cells and natural killer cells(NK cells).
- It is known for enhancing the activities of NK cells, proliferation and differentiation of B cells and T cells.
Interleukin-22(IL-22)
- IL-22 is typically synthesized by T lymphocytes but can also be produced by various innate and acquired immune cells.
- It suppresses the production of IL-4 and plays a role in tissue repair.
Interleukin-23(IL-23)
- IL-23 is principally made by antigen-presenting cells(dendritic cells) and macrophages.
- It monitors the perpetuation of IL-17 and regulates the production of T lymphocytes.
Interleukin-24(IL-24)
- IL-24 is mainly secreted by monocytes, T and B lymphocytes.
- It helps in the healing of wounds and also protects from pathogenic bacteria and cardiovascular diseases.
Interleukin-25(IL-25)
- IL-25 is mostly secreted by dendritic cells.
- It triggers the production of Th2 cytokine profile along with IL-4 and IL-13.
Interleukin-26(IL-26)
- IL-26 is secreted by Th17 cells.
- It acts as a stimulator and helps in the production of IL-1 beta, IL-6 and IL-8.
- Also helps in procreating the Th17 cells and is known in influencing the expression of IL-10.
Interleukin-27(IL-27)
- IL-27 is produced by T lymphocytes.
- It triggers the activation of STAT-1 and STAT-3 genes that are known to govern immune responses.
- It acts as a stimulator in producing IL-10 and plays a key role in the synthesis of type-2 IFN by NK cells.
Interleukin-28(IL-28)
- IL-28 is mainly released by regulatory T lymphocytes (TREG).
- It monitors the activities of keratinocytes and melanocytes.
- Plays a major role in triggering the viral antigenic cell presentation to cytotoxic T lymphocytes and upregulating the expressions of TLR-2 and TLR-3 protein molecules.
Interleukin-30(IL-30)
- IL-29 is synthesized by dendritic cells, regulatory T cells and by cells infected with a virus.
- It helps in upregulating the responses pertaining to viral protection.
Interleukin-31(IL-31)
- IL-31 is predominantly secreted by Th2 cells and dendritic cells.
- It induces chemokinesis of polymorphonuclear cells, monocytes and T lymphocytes to the region under inflammation.
- It triggers the production of the secretion of chemokines and the production of interleukin-6, interleukin-16 and interleukin-32.
Interleukin-32(IL-32)
- IL-32 is principally made by NK cells and monocytes.
- It stimulates the production of various cytokines such as interleukin-6 and interleukin-1 beta.
- It also helps in suppressing the secretion of IL-15.
Interleukin-33(IL-33)
- IL-33 is secreted by Th2 cells and mast cells.
- It aids protection against parasitic infections and type-1 hypersensitivity reactions.
Interleukin-34(IL-34)
- IL-34 is produced by epithelial cells and different types of phagocytes.
- It emphasizes the production of IL-6, helps in regulating the differentiation and development of antigen-presenting cells that are involved in triggering microglial cells–which are innate immune effector cells of the central nervous system.
Interleukin-35(IL-35)
- IL-35 is typically synthesized by regulatory B cells.
- It acts as an immunosuppressant agent and on the other hand, regulates the differentiation of lymphocytes.
Interleukin-36(IL-36)
- IL-36 is mostly secreted by phagocytes.
- It monitors the activities of T cells and natural killer cells and helps in governing the production of interferon gamma.
- It helps in the formation of cellular components of blood and secretion of intracellular adhesion molecules, MHC class I and class II molecules.
Interleukin-37(IL-37)
- IL-37 is secreted by the thymus, testis, uterus and phagocytes.
- It monitors the innate immune responses and helps in immunosuppression.
- In autoimmune disorders, IL-37 upregulates immune responses and inflammation.
Interleukin-38 (IL-38)
- IL-38 is principally released by the thymus, spleen, B-cells of tonsils, skin and placenta.
- It acts on T lymphocytes and suppresses the production of interleukin-17 and interleukin-22.
Interleukin-39 (IL-39)
- IL-39 is typically released by B-cells.
- It governs the activities of neutrophilic cells and triggers differentiation or expansion.
Interleukin-40(IL-40)
- IL-40 is synthesized by the fetal liver, activated B-cells and in the bone marrow.
- It crucially participates in the development of humoral immunity.
Mohammad Reshma
March 02, 2022
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