Cytokines
In medicine, cytokines are the primary intercellular chemical messengers of the immune system. Chemically, they are water-soluble proteins and glycoproteins with a mass of 8 to 30 kDaltons (kDa). These protein messengers are produced and released by cells of the immune system such as B-lymphocytes, macrophages and T-lymphocytes. Their actions are essential to the the activation and control of immune responses and the development of blood cells. Once they attach to the surface of a target cell, they may invoke a second messenger system, which causes a release, inside the cell, of chemical messenger(s) that cause specific activities. Those activities may include the extracellular release of additional, usually differentiated cytokines, so cells amplify cytokines. Mammalian cytokines are "non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner."[1] Examples include growth factors,interferons, interleukins, and tumor necrosis factor.
Plants may synthesize cytokines, which affect the plants, but some, such as abscisic acid, also affect humans.[2] In botany, however, the cytokinins are a group distinct from animal cytokines.
Cytokine is not the universal name for the group.[3] Other name refer to sources of specific kinds of cytokines, or their categorizing by target of action. Once the amino acid sequence of a cytokine is known, by convention, it is reclassified as an interleukin. [4]
Categorizing by source
They may be named by their source:
- lymphokine (cytokines made by lymphocytes)
- monokine (cytokines made by monocytes)
- chemokine (cytokines with chemotactic activities)
- interleukin (cytokines made by one leukocyte and acting on other leukocytes).
Categorizing by target
They also may be categorized by their target; some cytokines have more than one of the type:
- On the secreting cell: autocrine cytokine
- on nearby cells: paracrine
- on distant cells: endocrine action. This last group overlaps releasing factors and hormones.
Categorizing by structure
Structurally, cytokines can be classified into several classes: [5]
- four alpha-helix bundle family consisting of the IL-2 subfamily (including erythropoietin and thrombopoietin,
- interferon subfamily (approximately 20 α-interferon and 1 β-interferon in Type I, one β-interferon in Type II) and the IL-10 subfamily[6]
- IL-1 family (primarily IL-1 and IL-18)
- IL-17 family
- chemokine family
Categorizing by receptor
- Immunoglobulin (Ig-x) superfamily are found throughout the body (eg, IL-1 receptor types)
- Interferon (type 2) family includes IFN beta and gamma receptors.
- Tumor necrosis factor (TNF) (type 3) family is composed of receptors sharing a cystein-rich extracellular binding domain and includes non-cytokine ligands such as CD40, CD27, and CD30 in addition to TNF.
- 7-transmembrane helix family that includes all G-protein coupled receptors (GPCRs), such as the chemokine receptors CXCR4 and CCR5 (HIV binding proteins) belong to this family.
Categorizing by hybrid, functional organization
Major chemical families include:
- Interleukins (IL) (formally called lymphocyte activating factor)
- Interferons (INF)
- Tumor necrosis factors (TNF)
- Granulocyte-Monocyte Colony Stimulating Factor
- Erythrocyte Stimulating Factor
- Macrophage chemotactic protein (MCP)
- Macrophage inflammatory protein (MIP)
| Name(s) | Source | Target | Function |
|---|---|---|---|
| Il-1a, IL-1b | monocytes, macrophages, B-lymphocytes, DC | Th cells, B cells, NK cells, general inflammation-susceptible | Th cell co-stimulation, B-lymphocyte maturation and proliferation, NK cell activation, general inflammation |
| IL-2 | Th1 cells | activated T- and B-lymphocytes, NK cells | growth, proliferation, activation |
| IL-3 | Th cells, NK cells | stem cells, mast cells | stem cell growth and differentiation, mast cells growth and histamine release |
| IL-4 | Th2 cells | activated B cells, macrophages, T cells | IgG1 and IgE synthesis ,macrophage MHC Class II, T cell growth, B cell growth |
| IL-5 | Th2 cells | activated B cells | proliferation and differentiation, IgA synthesis |
| IL-6 | monocytes, macrophages, T-helper subtype 2 lymphocytes (Th2 cells), stromal cells | activated B cells, plasma cells, stem cells, | differentiate B lymphocytes (B cells) into plasma cells, plasma cell antibody secretion, stem cell differentiation, general acute phase response, increases hepcidin secretion |
| IL-7 | marrow and thymus stroma | stem cells | differentiation |
| IL-8 | macrophages and endothelial cells | neutrophils | chemotaxic attraction of neutrophils |
| IL-10 | Th2 cells | macrophages, B-cells | downregulate cytokine production by macrophages, activate B-lymphocytes |
| IL-12 | macrophages, B cells | activated Tc cells, natural killer cells | In combination with IL-2, differentiate Tc cells into CTL; activate NK |
| IL-13 | TH2 cells | Similar to IL-4 | |
| GM-CSF | Th cells | progenitor cells | growth and differentiation of monocytes and dendritic cells (DC) |
References
- ↑ Anonymous (2024), Cytokines (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Nicole LeBrasseur (23 April 2007), "Plant hormone is human cytokine", J Cell Biol 177, DOI:10.1083/jcb.1772rr1.
- ↑ Decker, Janet, Cytokines, Welcome to webImmunology 419!, University of Arizona
- ↑ Ganong, William F. (Nineteenth edition, 1999), Review of Medical Physiology, Appleton & Lange,pp. 498-499
- ↑ What are cytokines?, Ion Channel Media Group Ltd.
- ↑ The International Society for Interferon and Cytokine Research (ISICR), Interferons: A primer for the non-scientist