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Cytokines are a category of less-widely-known signalling proteins and glycoproteins that, like hormones and neurotransmitters, are used extensively in cellular communication. While hormones are secreted from specific organs to the blood, and neurotransmitters are related to neural acitivity, 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 kDa. Image File history File links Broom_icon. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... A glycoprotein is a macromolecule composed of a protein and a carbohydrate (a sugar). ... Hormone is also the NATO reporting name for the Soviet/Russian Kamov Ka-25 military helicopter. ... Neurotransmitters are chemicals that are used to relay, amplify and modulate electrical signals between a presynaptic and a postsynaptic neuron. ... This article needs to be cleaned up to conform to a higher standard of quality. ... Red blood cells (erythrocytes) are present in the blood and help carry oxygen to the rest of the cells in the body Blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). ... The atomic mass unit (amu), unified atomic mass unit (u), or dalton (Da), is a small unit of mass used to express atomic masses and molecular masses. ...

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. A pathogen (from Greek pathos, suffering/emotion, and gene, to give birth to), infectious agent, or more commonly germ, is a biological agent that causes disease or illness to its host. ... A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... Embryogenesis is the process by which the embryo is formed and develops. ...

Effects

Each cytokine binds to a specific cell-surface receptor. Subsequent 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 feedback inhibition. In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... A biochemical cascade is a series of chemical reactions in which the products of one reaction are consumed in the next reaction. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... In the context of genetics, a transcription factor is a regulatory protein that initiates the transcription of certain genes upon binding with DNA. The binding of a transcription factor to a specific DNA sequence can result in either an increased rate of transcription of the gene, known as activated transcription... HIV protease in a complex with the protease inhibitor ritonavir. ...

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, if the cytokine acts on the cell that secretes it
• paracrine, if the action is restricted to the immediate vicinity of a cytokine's secretion
• 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 antibodies have a stronger immune effect than the cytokine alone. This may lead to lower therapeutic doses and perhaps fewer side-effects. Autocrine signaling is a form of signalling in which a cell secretes a chemical messenger (called the autocrine agent) that signals the same cell. ... Paracrine signaling is a form of cell signaling in which the target cell is close to (para = alongside of or next to, but this strict prefix definition is not meticulously followed here) the signal releasing cell. ... Major endocrine glands. ... Each antibody binds to a specific antigen; an interaction similar to a lock and key. ...

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. A cytokine storm is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells. ... TGN1412 (also known as CD28-SuperMAB) is the working name of an immunomodulatory drug which was withdrawn from development, originally intended for the treatment of B cell chronic lymphocytic leukemia (B-CLL) and rheumatoid arthritis. ...

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. Lymphokines are a subset of Cytokines that are produced by immune cells. ... Interleukins are a group of cytokines that are expressed by white blood cells (leukocytes, hence the -leukin) as a means of communication (inter-). The function of the immune system depends in a large part on interleukins, and rare deficiencies of a number of them have been described, all featuring autoimmune... Chemokines are a class of chemotactic cytokines, or small secreted protein signals. ...

• The term interleukin was initially used by researchers for those cytokines whose presumed targets are principally 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 cells.
• 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. White Blood Cells redirects here. ... Chemotaxis is a kind of taxis, in which bodily cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. ... Interleukin-8 (IL-8) is a chemokine produced by macrophages and other cell types such as epithelial cells. ...

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:

• The four α-helix bundle family - Member cytokines have three-dimensional structures with four bundles of α-helices. This family in turn is divided into three sub-families:
  1. the IL-2 subfamily
  2. the interferon (IFN) subfamily
  3. the IL-10 subfamily.
  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.
• the IL-1 family, which primarily includes IL-1 and IL-18
• the 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
• Chemokines.

Side view of an α-helix of alanine residues in atomic detail. ... Interleukin-2 (IL-2) is an interleukin, a type of biological response modifier, a substance that can improve the bodys natural response to disease. ... Interferons (IFNs) are natural proteins produced by the cells of the immune system of most vertebrates in response to challenges by foreign agents such as viruses, bacteria, parasites and tumor cells. ... Interleukin-10 (IL-10 or IL10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine, capable of inhibiting synthesis of pro-inflammatory cytokines like IFN-gamma, IL-2, IL-3, TNFα and GM-CSF by cells such as macrophages and Th1 cells. ... Erythropoietin (IPA pronunciation: , alternative pronunciations: ) or EPO is a glycoprotein hormone that is a cytokine for erythrocyte (red blood cell) precursors in the bone marrow. ... Thrombopoietin is the recently discovered (1994) glycoprotein hormone that regulates the production of platelets. ... Interleukin-1 (IL-1) is secreted by the macrophages, monocytes and dendritic cells. ... Interleukins are a group of cytokines that were first seen to be expressed by white blood cells (leukocytes, hence the -leukin) as a means of communication (inter-). The name is sort of a relic though; it has since been found that interleukins are produced by a wide variety of bodily... Interleukins are a group of cytokines that were first seen to be expressed by white blood cells (leukocytes, hence the -leukin) as a means of communication (inter-). The name is sort of a relic though; it has since been found that interleukins are produced by a wide variety of bodily... Chemokines are a class of chemotactic cytokines, or small secreted protein signals. ...

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 (IL-4, IL-10, IL-13, etc.), which favor antibody responses. Interleukin-4, abbreviated IL-4, is a Cytokine that stimulates the proliferation of activated B-cells, T-cells, and differentiation of CD4+T-cells into Th2 cells, among other effects. ... Interleukin-10 (IL-10 or IL10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine, capable of inhibiting synthesis of pro-inflammatory cytokines like IFN-gamma, IL-2, IL-3, TNFα and GM-CSF by cells such as macrophages and Th1 cells. ... Interleukin 13 (IL-13) is a cytokine secreted by many cell types, but especially T helper type 2 (Th2) cells, that is an important mediator of allergic inflammation and disease. ...

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 disorders. Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ...

Cytokine receptors

Main article: 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. Key steps of the JAK-STAT pathway A Cytokine receptor is a receptor which binds cytokines. ...

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 (Ig) superfamily, which are ubiquitously present throughout several cells and tissues of the vertebrate body, and share structural homology with immunoglobulins (antibodies), cell adhesion molecules, 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).
• 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.

Cell Adhesion Molecules (CAMs) are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix (ECM) in the process called cell adhesion. ... In biology, homology is any similarity between structures that is due to their shared ancestry. ... Each antibody binds to a specific antigen; an interaction similar to a lock and key. ... Cell Adhesion Molecules (CAMs) are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix (ECM) in the process called cell adhesion. ... Growth factor is a protein that acts as a signaling molecule between cells (like cytokines and hormones) that attaches to specific receptors on the surface of a target cell and promotes differentiation and maturation of these cells. ... This article is about the class of chemicals. ... Severe combined immunodeficiency, or SCID, is a genetic disorder in which both arms (B cells and T cells) of the adaptive immune system are crippled, due to a defect in one of several possible genes. ... X-linked Severe Combined Immunodeficiency (X-SCID) is a profound and severe immunodeficiency characterized by the complete absence of NK cells and T cells in the peripheral blood. ... Interferons (IFNs) are natural proteins produced by the cells of the immune system of most vertebrates in response to challenges by foreign agents such as viruses, bacteria, parasites and tumor cells. ... Tumor necrosis factors (or the TNF-family) refers to a group of cytokines family which can cause apoptosis. ... Cysteine is a naturally occurring, sulfur-containing amino acid that is found in most proteins, although only in small quantities. ... In chemistry, a ligand is an atom, ion or functional group that is bonded to one or more central atoms or ions, usually metals generally through co-ordinate covalent bond. ... CD40 is a costimulatory protein found on antigen presenting cells. ... CD27 is a tumor necrosis factor receptor. ... Cluster of differentiation (CD) molecules are markers on the cell surface, as recognized by specific sets of antibodies, used to identify the cell type, stage of differentiation and activity of a cell. ... In cell biology, G-protein-coupled receptors, also known as GPCR, seven transmembrane receptors, heptahelical receptors, or 7TM receptors, are a class of transmembrane receptors. ... Wikipedia does not yet have an article with this exact name. ... Species Human immunodeficiency virus 1 Human immunodeficiency virus 2 Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS, a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections). ... CXCR4, also called fusin, is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1). ... CCR5, short for chemokine (C-C motif) receptor 5, is a chemokine receptor. ...

Cysteine-knot cytokines

Members of the transforming growth factor beta superfamily belong to this group, including TGF-β1, TGF-β2 and TGF-β3. The transforming growth factor beta (TGF-β) superfamily is a large family of structurally related cell regulatory proteins that was named after its first member, TGF-β1, originally described in 1983[1]. Many proteins have since been described as members of the TGF-β superfamily in a variety of species, including invertebrates... Transforming growth factor beta 1 or TGFβ1 is a polypeptide member of the Transforming growth factor beta superfamily of ligands. ... TGF2 is a secreted protein that performs many cellular functions. ... TGF3 is involved in cell differentiation and embryogenesis. ...

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Image File history File links This is a lossless scalable vector image. ...

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 Vol. 311 No. 5769, pp. 1875 - 1876, 31 March 2006 DOI: 10.1126/science.1126030

Science is the journal of the American Association for the Advancement of Science (AAAS). ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

See also

• Adipokines
• Apoptosis
• Chemokines
• Cytokine secretion assay
• Cytokine storm
• ELISA assays
• ELISPOT assays
• Interleukins
• Interferon
• Granulocyte-colony stimulating factor
• Signal transduction
• Tumor necrosis factors

The adipokines or adipocytokines are a group of cytokines (cell-to-cell signalling proteins) secreted by adipose tissue. ... A section of mouse liver showing an apoptotic cell indicated by an arrow Apoptosis (pronounced apo tō sis) is a process of suicide by a cell in a multicellular organism. ... Chemokines are a family of pro-inflammatory activation-inducible cytokines, or small protein signals secreted by cells. ... Secretion assay is a process used in cell biology to identify cells that are secreting a particular protein (usually a cytokine). ... A cytokine storm is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells. ... Elisa (born Elisa Toffoli on 19 December 1977) is an Italian singer and solo artist, writing and performing within several genres, notably rock, blues, soul and ambient. ... The Enzyme-linked immunosorbent spot (ELISPOT) is a common method for monitoring immune responses in humans and animals. ... Interleukins are a group of cytokines that were first seen to be expressed by white blood cells (leukocytes, hence the -leukin) as a means of communication (inter-). The name is sort of a relic though; it has since been found that interleukins are produced by a wide variety of bodily... Interferons (IFNs) are natural proteins produced by the cells of the immune system of most vertebrates in response to challenges by foreign agents such as viruses, bacteria, parasites and tumor cells. ... Insert non-formatted text hereGranulocyte-Colony Stimulating Factor (G-CSF) is a glycoprotein, growth factor or cytokine produced by a number of different tissues to stimulate the bone marrow to produce granulocytes. ... In biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another, most often involving ordered sequences of biochemical reactions inside the cell, that are carried out by enzymes and linked through second messengers resulting in what is thought of as... Tumor necrosis factors (or the TNF-family) refers to a group of cytokines family which can cause apoptosis. ...

External links

• Cytokine Tutorial
• Cell Interactions: Cytokines
• Reperfusion Injury in Stroke.
• Cytokines Online Pathfinder Encyclopaedia
• Cytokines and inflammation, science and practical journal