Cytokine 153663 220793299 2008-06-21T16:35:52Z Sherry Vapors 2136249 Corrected "acitivity" to "activity" in paragrpah 1. {{Cleanup|date=June 2007}} '''Cytokines''' are a category of signalling [[proteins]] and [[glycoproteins]] that, like [[hormones]] and [[neurotransmitters]], are used extensively in [[cell communication|cellular communication]]. While hormones are secreted from specific organs to the blood, and neurotransmitters are related to neural activity, the cytokines are a more diverse class of compounds in terms of origin and purpose. They are produced by a wide variety of [[hematopoietic]] and non-hematopoietic cell types and can have effects on both nearby cells or throughout the organism, sometimes strongly dependent on the presence of other chemicals. The cytokine family consists mainly of smaller, water-soluble proteins and glycoproteins with a mass of between 8 and 30 [[Kilodalton|kDa]]. Cytokines are critical to the functioning of both innate and adaptive immune responses. They are often secreted by immune cells which have encountered a [[pathogen]] as a way to activate and recruit more immune cells and increase the system's response to the pathogen. However, apart from their role in the development and functioning of the [[immune system]], as well as their aberrant modes of secretion in a variety of immunological, inflammatory and infectious diseases, cytokines are also involved in several developmental processes during [[embryogenesis]]. ==Effects== Each cytokine binds to a specific [[Receptor (biochemistry)|cell-surface receptor]]. Subsequent [[biochemical cascade|cascades]] of intracellular signaling then alter cell functions. This may include the upregulation and/or downregulation of several [[genes]] and their [[transcription factors]], in turn resulting in the production of other cytokines, an increase in the number of surface receptors for other molecules, or the suppression of their own effect by [[enzyme inhibitor|feedback inhibition]]. The effect of a particular cytokine on a given cell depends on the cytokine, its extracellular abundance, the presence and abundance of the complementary receptor on the cell surface, and downstream signals activated by receptor binding; these last two factors can vary by cell type. Cytokines are characterized by considerable "redundancy", in that many cytokines appear to share similar functions. Generalization of functions is not possible with cytokines; nonetheless, their actions may be grouped as: *[[autocrine signalling|autocrine]], if the cytokine acts on the cell that secretes it *[[paracrine signalling|paracrine]], if the action is restricted to the immediate vicinity of a cytokine's secretion *[[endocrine system|endocrine]], if the cytokine diffuses to distant regions of the body (carried by blood or plasma) to affect different tissues. It seems to be a paradox that cytokines binding to [[antibody|antibodies]] have a stronger immune effect than the cytokine alone. This may lead to lower therapeutic doses and perhaps fewer side-effects. Overstimulation of cytokines can trigger a dangerous syndrome known as a [[cytokine storm]]; this may have been the cause of severe adverse events during a clinical trial of [[TGN1412]]. ==Nomenclature== Cytokines have been variously named as [[lymphokines]], [[interleukins]], and [[chemokines]], based on their presumed function, cell of secretion, or target of action. Because cytokines are characterized by considerable redundancy and pleiotropism, such distinctions, allowing for exceptions, are obsolete. * The term ''interleukin'' was initially used by researchers for those cytokines whose presumed targets are principally [[White blood cell|leukocytes]]. It is now used largely for designation of newer cytokine molecules discovered every day and bears little relation to their presumed function. The vast majority of these are produced by [[T-helper cell]]s. * The term ''chemokine'' refers to a specific class of cytokines that mediates chemoattraction ([[chemotaxis]]) between cells. IL-8 ([[interleukin-8]]) is the only chemokine originally named an interleukin. ==Classification== ===Structural=== Structural homology has been able to partially distinguish between cytokines that do not demonstrate a considerable degree of redundancy so that they can be classified into four types: <ul> <li>The [[four α-helix bundle family]] - Member cytokines have three-dimensional structures with four bundles of [[alpha helix|α-helices]]. This family in turn is divided into three sub-families: <ol> <li> the [[interleukin 2|IL-2]] subfamily <li> the [[interferon|interferon (IFN)]] subfamily <li> the [[interleukin 10|IL-10]] subfamily. </ol>The first of these three subfamilies is the largest. It contains several non-immunological cytokines including [[erythropoietin]] (EPO) and [[thrombopoietin]] (THPO). Also, four α-helix bundle cytokines can be grouped into ''long-chain'' and ''short-chain'' cytokines. <li> the [[interleukin 1|IL-1]] family, which primarily includes IL-1 and [[interleukin|IL-18]] <li> the [[interleukin 17|IL-17]] family, which has yet to be completely characterized, though member cytokines have a specific effect in promoting proliferation of T-cells that cause cytotoxic effects <li> [[Chemokines]]. </ul> ===Functional=== A classification that proves more useful in clinical and experimental practice divides immunological cytokines into those that enhance cytokine responses, type 1 ( IFN-γ, TGF-β etc.), and type 2 ([[interleukin 4|IL-4]], [[interleukin 10|IL-10]], [[interleukin 13|IL-13]], etc.), which favor antibody responses. A key focus of interest has been that cytokines in one of these two sub-sets tend to inhibit the effects of those in the other. Dysregulation of this tendency is under intensive study for its possible role in the pathogenesis of [[autoimmune disorder]]s. == Cytokine receptors == {{Main|Cytokine receptor}} In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors has now been directly linked to certain debilitating immunodeficiency states. In this regard, and also because the redundancy and pleiomorphism of cytokines are, in fact, a consequence of their homologous receptors, many authorities are now of the opinion that a classification of cytokine receptors would be more clinically and experimentally useful. A classification of cytokine receptors based on their three-dimensional structure has, therefore, been attempted. Such a classification, though seemingly cumbersome, provides several unique perspectives for attractive pharmacotherapeutic targets. * [[Immunoglobulin superfamily|Immunoglobulin (Ig) superfamily]], which are ubiquitously present throughout several cells and tissues of the vertebrate body, and share structural [[homology (biology)|homology]] with immunoglobulins ([[antibody|antibodies]]), [[cell adhesion molecule]]s, and even some cytokines. Examples: IL-1 receptor types. * Haemopoietic [[Growth Factor]] (type 1) family, whose members have certain conserved motifs in their extracellular [[amino-acid]] domain. The IL-2 receptor belongs to this chain, whose γ-chain (common to several other cytokines) deficiency is directly responsible for the x-linked form of [[Severe Combined Immunodeficiency]] ([[X-SCID]]). * [[Interferon]] (type 2) family, whose members are receptors for IFN β and γ. * [[Tumor necrosis factors]] (TNF) (type 3) family, whose members share a [[cysteine]]-rich common extracellular binding domain, and includes several other non-cytokine [[ligands]] like [[CD40]], [[CD27]] and [[CD30]], besides the ligands on which the family is named (TNF). * [[7TM Receptor|Seven transmembrane helix]] family, the ubiquitous receptor type of the animal kingdom. All [[G-protein coupled receptors]] (for hormones and neurotransmitters) belong to this family. Chemokine receptors, two of which act as binding proteins for [[HIV]] ([[CXCR4]] and [[CCR5]]), also belong to this family. == Cysteine-knot cytokines == Members of the [[transforming growth factor beta superfamily]] belong to this group, including [[TGF beta 1|TGF-β1]], [[TGF beta 2|TGF-β2]] and [[TGF beta 3|TGF-β3]]. {{Expand-section|date=February 2007}} ==References== * Gallin J, Snyderman R (eds). Inflammation: Basic Principles and Clinical Correlates. 3rd edition, Philadelphia, Lippincott William and Wilkins, 1999. * Janeway CA et al. (eds). Immunobiology. The immune system in Health and Disease, 4th edition, New York, Garland, 1999. * Roitt I et al. (eds.) Immunology. 5th edition, London, Mosby, 2002. * ''[[Science (journal)|Science]]'' Vol. 311 No. 5769, pp. 1875 - 1876, 31 March 2006 [[Digital object identifier|DOI]]: [http://dx.doi.org/10.1126/science.1126030 10.1126/science.1126030] == See also == * [[Adipokine]]s * [[Apoptosis]] * [[Chemokine]]s * [[Secretion assay|Cytokine secretion assay]] * [[Cytokine storm]] * [[ELISA]] assays * [[ELISPOT]] assays * [[Interleukin]]s * [[Interferon]] * [[Granulocyte-colony stimulating factor]] * [[Signal transduction]] * [[Tumor necrosis factors]] ==External links== *[http://microvet.arizona.edu/Courses/MIC419/Tutorials/cytokines.html Cytokine Tutorial] *[http://www-immuno.path.cam.ac.uk/~immuno/part1/lec09/lec10_99.html Cell Interactions: Cytokines] *[http://www.emedicine.com/neuro/topic602.htm Reperfusion Injury in Stroke]. *[http://www.copewithcytokines.de Cytokines Online Pathfinder Encyclopaedia] *[http://www.cytokines.ru Cytokines and inflammation, science and practical journal] {{Cell_signaling}} {{Immune system}} {{Cytokines}} {{Chemokines}} {{Interleukins}} [[Category:Cytokines| ]] [[de:Zytokin]] [[es:Citocina]] [[fr:Cytokine]] [[ko:사이토카인]] [[it:Citochina]] [[he:ציטוקין]] [[nl:Cytokine]] [[ja:サイトカイン]] [[pl:Cytokiny]] [[pt:Citocina]] [[ru:Цитокины]] [[simple:Cytokine]] [[fi:Sytokiini]] [[sl:Citokin]] [[sv:Cytokiner]] [[vi:Cytokine]] [[tr:Sitokin]] [[zh:细胞因子]]