48-565: 1HIB , 1I1B , 1IOB , 1ITB , 1L2H , 1S0L , 1T4Q , 1TOO , 1TP0 , 1TWE , 1TWM , 21BI , 2I1B , 2KH2 , 2NVH , 31BI , 3O4O , 3POK , 41BI , 4DEP , 4G6J , 4G6M , 4GAI , 4I1B , 5I1B , 6I1B , 7I1B , 9ILB , 4GAF , 5BVP 3553 16176 ENSG00000125538 ENSMUSG00000027398 P01584 P10749 NM_000576 NM_008361 NP_000567 NP_032387 Interleukin-1 beta ( IL-1β ) also known as leukocytic pyrogen , leukocytic endogenous mediator , mononuclear cell factor , lymphocyte activating factor and other names,
96-432: A classification, though seemingly cumbersome, provides several unique perspectives for attractive pharmacotherapeutic targets. Each cytokine has a matching 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 , resulting in the production of other cytokines, an increase in
144-493: A considerable degree of redundancy so that they can be classified into four types: A classification that proves more useful in clinical and experimental practice outside of structural biology divides immunological cytokines into those that enhance cellular immune responses , type 1 (TNFα, IFN-γ, etc.), and those that enhance antibody responses, type 2 (TGF-β, IL-4 , IL-10, IL-13 , etc.). A key focus of interest has been that cytokines in one of these two sub-sets tend to inhibit
192-489: A deficiency of cytokine receptors has now been directly linked to certain debilitating immunodeficiency states. In this regard, and also because the redundancy and pleomorphism of cytokines are, in fact, a consequence of their homologous receptors, many authorities think 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
240-468: A feature that differentiates them from hormones. Virtually all nucleated cells, but especially endo/epithelial cells and resident macrophages (many near the interface with the external environment) are potent producers of IL-1 , IL-6 , and TNF-α . In contrast, classic hormones, such as insulin , are secreted from discrete glands such as the pancreas . The current terminology refers to cytokines as immunomodulating agents . A contributing factor to
288-408: A nucleotide-binding domain and a leucine-rich repeat ) type of inflammasome is activated by various stimuli and there are documented several diseases connected to NLRP3 activation like type 2 diabetes mellitus , Alzheimer's disease , obesity and atherosclerosis . Before cleavage by caspase 1, pro-IL-1β has a molecular weight of 37 kDa . The molecular weight of the proteolytically processed IL-1β
336-477: A paradox that cytokines binding to antibodies have a stronger immune effect than the cytokine alone. This may lead to lower therapeutic doses. It has been shown that inflammatory cytokines cause an IL-10-dependent inhibition of T-cell expansion and function by up-regulating PD-1 levels on monocytes, which leads to IL-10 production by monocytes after binding of PD-1 by PD-L. Adverse reactions to cytokines are characterized by local inflammation and/or ulceration at
384-486: A significant effect. The role of IL-1β in age-related macular degeneration has not been proven in patient, but in many animal models and in vitro studies it has been demonstrated the role of IL-1β in retinal pigmented epithelial cells and photoreceptor cells damage. NLRP3 inflammasome activate caspase-1 which catalyze cleavage of inactive cytosolic precursor pro-IL-1β to its mature form IL-1β. Retinal pigmented epithelial cells forms blood retinal barrier in human retina which
432-402: A subset of dendritic cells known as slanDC, as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response , and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis . The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in
480-425: Is 17.5 kDa. IL-1β has the following amino acid sequence: The physiological activity determined from the dose dependent proliferation of murine D10S cells is 2.5 x 10 to 7.1 x 10 units/mg. IL-1β is present in other species of animals, however non-mammalian sequences of IL-1β lack a conserved cascase-1 cleavage site. Increased production of IL-1β causes a number of different autoinflammatory syndromes , most notably
528-540: Is a cytokine protein that in humans is encoded by the IL1B gene . There are two genes for interleukin-1 (IL-1): IL-1 alpha and IL-1 beta (this gene). IL-1β precursor is cleaved by cytosolic caspase 1 (interleukin 1 beta convertase) to form mature IL-1β. The fever-producing property of human leukocytic pyrogen (interleukin 1) was purified by Dinarello in 1977 with a specific activity of 10–20 nanograms/kg. In 1979, Dinarello reported that purified human leukocytic pyrogen
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#1732872792928576-544: Is a human monoclonal antibody targeted at IL-1B, and approved in many countries for treatment of cryopyrin-associated periodic syndromes . Rilonacept is an IL-1 trap developed by Regeneron targeting IL-1B, and approved in the US as Arcalyst. Because many authors of scientific manuscripts make the minor error of using a homoglyph , sharp s (ß), instead of beta (β), mentions of "IL-1ß" [sic] often become "IL-1ss" [sic] upon automated transcoding (because ß transcodes to ss). This
624-419: Is a recombinant and slightly modified version of the human interleukin 1 receptor antagonist protein. Anakinra blocks the biologic activity of IL-1 alpha and beta by competitively inhibiting IL-1 binding to the interleukin type 1 receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. Anakinra is marketed as Kineret and is approved in the US for treatment of RA, NOMID, DIRA . Canakinumab
672-436: Is believed that Neanderthals and Denisovans had twenty-three pairs. Human chromosome 2 is a result of an end-to-end fusion of two ancestral chromosomes. The evidence for this includes: We conclude that the locus cloned in cosmids c8.1 and c29B is the relic of an ancient telomere-telomere fusion and marks the point at which two ancestral ape chromosomes fused to give rise to human chromosome 2. The following are some of
720-616: Is connected to malignancies such as colon cancer and melanoma. It was reported that IL-1β secretion was elevated in the lung adenocarcinoma cell line A549. It has also been shown in another study that IL-1β, together with IL-8, plays an important role in chemoresistance of malignant pleural mesothelioma by inducing expression of transmembrane transporters. Another study showed that inhibition of inflammasome and IL-1β expression decreased development of cancer cells in melanoma. Furthermore, it has been found that in breast cancer cells, IL-1β activates p38 and p42/22 MAPK pathways which ultimately lead to
768-535: Is important for retinal metabolic activity, integrity and inhibition of immune cells infiltration. It has been shown that human retinal pigmented epithelial cells can secrete IL-1 β in exposure to oxidative stress . The inflammatory reaction leads to damage of retinal cells and infiltration of cells of the immune system. The inflammatory process including NLRP3 upregulation is one of the causes of age-related macular degeneration and other retinal diseases that lead to vision loss. Additionally, it has been shown that caspase-1
816-506: Is not known exactly which cells produce IL-1β. Treatment of multiple sclerosis with glatiramer acetate or natalizumab has also been shown to reduce the presence of IL-1β or its receptor. Several types of inflammasomes are suggested to play role in tumorgenesis due to their immunomodulatory properties, modulation of gut microbiota, differentiation and apoptosis. Over-expression of IL-1β caused by inflammasome may result in carcinogenesis. Some data suggest that NLRP3 inflammasome polymorphisms
864-521: Is one of the twenty-three pairs of chromosomes in humans . People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost eight percent of the total DNA in human cells . Chromosome 2 contains the HOXD homeobox gene cluster. Humans have only twenty-three pairs of chromosomes, while all other extant members of Hominidae have twenty-four pairs. It
912-433: Is preserved by feedback interactions between diverse cell types mediated by adhesion molecules and secreted cytokines; disruption of normal feedback mechanisms in cancer threatens tissue integrity. Over-secretion of cytokines can trigger a dangerous cytokine storm syndrome . Cytokine storms may have been the cause of severe adverse events during a clinical trial of TGN1412 . Cytokine storms are also suspected to have been
960-494: Is upregulated in the retina of diabetic patients, causing a higher production of IL-1β and subsequent death of retinal neurons. Studies in mice on experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS) research, have found that blocking IL-1β could make the animals resistant to EAE. IL-1β led to the production of an antigen-specific pro-inflammatory subset of T helper cells ( T H17 ). In combination with other cytokines, interleukin-1β can upregulate
1008-493: Is why so many mentions of the latter appear in web search results. This article incorporates text from the United States National Library of Medicine , which is in the public domain . Cytokine Cytokines (/'saɪ.tə.kaɪn/) are a broad and loose category of small proteins (~5–25 kDa ) important in cell signaling . Due to their size, cytokines cannot cross the lipid bilayer of cells to enter
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#17328727929281056-503: The COVID-19 pandemic , some deaths from COVID-19 have been attributable to cytokine release storms. Current data suggest cytokine storms may be the source of extensive lung tissue damage and dysfunctional coagulation in COVID-19 infections. Some cytokines have been developed into protein therapeutics using recombinant DNA technology. Recombinant cytokines being used as drugs as of 2014 include: Chromosome 2 Chromosome 2
1104-709: The central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2 . IL-1β, in combination with IL-23 , induced expression of IL-17 , IL-21 and IL-22 by γδ T cells . This induction of expression is in the absence of additional signals. That suggests IL-1β is involved in modulation of autoimmune inflammation Different inflammasome complex — cytosolic molecular complex — have been described. Inflammasomes recognize danger signals and activate proinflammatory process and production of IL-1β and IL-18. NLRP3 (contains three domain: pyrin domain ,
1152-449: The cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptors on the target cell surface. Cytokines have been shown to be involved in autocrine , paracrine and endocrine signaling as immunomodulating agents . Cytokines include chemokines , interferons , interleukins , lymphokines , and tumour necrosis factors , but generally not hormones or growth factors (despite some overlap in
1200-597: The lamina propria . Here, the pathogens can further activate local immune cells and amplify the inflammatory response. It has been shown that IL-1 family plays important role in inflammation in many degenerative diseases, such as age-related macular degeneration , diabetic retinopathy and retinitis pigmentosa . Significantly increased protein level of IL-1β has been found in the vitreous of diabetic retinopathy patient. The role of IL-1β has been investigated for potential therapeutic target for treatment of diabetic retinopathy. However, systemic using of canakinumab did not have
1248-800: The MD geneticist Stanley Norman Cohen ) published an article describing the production of MIF in virus-infected allantoic membrane and kidney cells, showing its production is not limited to immune cells. This led to his proposal of the term cytokine. In 1993, Ogawa described the early acting growth factors, intermediate acting growth factors and late acting growth factors. Classic hormones circulate in aqueous solution in nanomolar (10 M) concentrations that usually vary by less than one order of magnitude . In contrast, some cytokines (such as IL-6 ) circulate in picomolar (10 M) concentrations that can increase up to 1,000 times during trauma or infection . The widespread distribution of cellular sources for cytokines may be
1296-454: The T H cell can become abortively infected, where the virus gets detected inside the cell and a programmed cell-death, known as pyroptosis , kills the infected cell. Pyroptosis is mediated via caspase-1 and is characterized by cell lysis and the secretion of IL-1β causing inflammation and attraction of more immune cells. This can create a cycle of CD4 T cells getting abortively infect with HIV, dying of pyroptosis, new T helper cells arriving to
1344-483: The activation of microglia . Consequently, microglia release interleukin-1β among other cytokines. Nevertheless, the significance of IL-1β in Alzheimer disease and the onset of neuroinflammation still remains largely unknown. Lastly, in vitro studies have shown that IL-1β causes an increase in mitochondrial glutaminase activity. In response, there is excessive glutamate secretion which has a neurotoxic effect. Anakinra
1392-744: The aged population can lead to inflammaging , and render these individuals more vulnerable to age-related diseases like neurodegenerative diseases and type 2 diabetes. A 2019 review was inconclusive as to whether cytokines play any definitive role in ME/CFS . A 2024 study found a positive correlation between plasma interleukin IL-2 and fatigue in patients with type 1 narcolepsy . Adverse effects of cytokines have been linked to many disease states and conditions ranging from schizophrenia , major depression and Alzheimer's disease to cancer . T regulatory cells ( Tregs ) and related-cytokines are effectively engaged in
1440-471: The ancient Greek language : cyto , from Greek κύτος, kytos , 'cavity, cell' + kines , from Greek κίνησις, kinēsis , 'movement'. Interferon-alpha, an interferon type I , was identified in 1957 as a protein that interfered with viral replication. The activity of interferon-gamma (the sole member of the interferon type II class) was described in 1965; this was the first identified lymphocyte -derived mediator. Macrophage migration inhibitory factor (MIF)
1488-607: The balance between humoral and cell-based immune responses, and they regulate the maturation, growth, and responsiveness of particular cell populations. Some cytokines enhance or inhibit the action of other cytokines in complex ways. They are different from hormones , which are also important cell signaling molecules. Hormones circulate in higher concentrations, and tend to be made by specific kinds of cells. Cytokines are important in health and disease, specifically in host immune responses to infection , inflammation , trauma , sepsis , cancer , and reproduction. The word comes from
Interleukin 1 beta - Misplaced Pages Continue
1536-846: The difficulty of distinguishing cytokines from hormones is that some immunomodulating effects of cytokines are systemic ( i.e. , affecting the whole organism) rather than local. For instance, to accurately utilize hormone terminology, cytokines may be autocrine or paracrine in nature, and chemotaxis , chemokinesis and endocrine as a pyrogen . Essentially, cytokines are not limited to their immunomodulatory status as molecules. Cytokines have been classed as lymphokines , interleukins , and chemokines , based on their presumed cell of secretion, function, or target of action. Because cytokines are characterised by considerable redundancy and pleiotropism , such distinctions, allowing for exceptions, are obsolete. Structural homogeneity has been able to partially distinguish between cytokines that do not demonstrate
1584-477: 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 . Several inflammatory cytokines are induced by oxidative stress . The fact that cytokines themselves trigger the release of other cytokines and also lead to increased oxidative stress makes them important in chronic inflammation , as well as other immunoresponses, such as fever and acute phase proteins of
1632-438: The gene count estimates of human chromosome 2. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome vary. Among various projects, the collaborative consensus coding sequence project ( CCDS ) takes an extremely conservative strategy. So CCDS's gene number prediction represents a lower bound on the total number of human protein-coding genes. The following
1680-446: The gut is an interface between symbiotic gut microbes that should remain with the host and pathogenic bacteria that should not gain access into the circulatory system. If HIV-infection leads to the secretion of IL-1βin monocytes and macrophages, it causes inflammation of this area. The mucosal epithelial layer responds to this by producing less or altering the tight junction proteins which makes it easier for pathogenic microbes to move into
1728-603: The injection sites. Occasionally such reactions are seen with more widespread papular eruptions . Cytokines are involved in several developmental processes during embryonic development . Cytokines are released from the blastocyst , and are also expressed in the endometrium , and have critical roles in the stages of zona hatching , and implantation . Cytokines are crucial for fighting off infections and in other immune responses. However, they can become dysregulated and pathological in inflammation , trauma, sepsis , and hemorrhagic stroke . Dysregulated cytokine secretion in
1776-486: The liver (IL-1,6,12, IFN-a). Cytokines also play a role in anti-inflammatory pathways and are a possible therapeutic treatment for pathological pain from inflammation or peripheral nerve injury. There are both pro-inflammatory and anti-inflammatory cytokines that regulate this pathway. 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
1824-520: The main cause of death in the 1918 "Spanish Flu" pandemic . Deaths were weighted more heavily towards people with healthy immune systems, because of their ability to produce stronger immune responses, with dramatic increases in cytokine levels. Another example of cytokine storm is seen in acute pancreatitis . Cytokines are integral and implicated in all angles of the cascade, resulting in the systemic inflammatory response syndrome and multi-organ failure associated with this intra-abdominal catastrophe. In
1872-436: The monogenic conditions referred to as Cryopyrin-Associated Periodic Syndromes (CAPS) , due to mutations in the inflammasome receptor NLRP3 which triggers processing of IL-1β. Intestinal dysbiosis has been observed to induce osteomyelitis through a IL-1β dependent manner. The presence of IL-1β has been also found in patients with multiple sclerosis (a chronic autoimmune disease of the central nervous system). However, it
1920-530: The number of surface receptors for other molecules, or the suppression of their own effect by 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. It seems to be
1968-448: The process of tumor immune escape and functionally inhibit immune response against the tumor. Forkhead box protein 3 ( Foxp3 ) as a transcription factor is an essential molecular marker of Treg cells. Foxp3 polymorphism (rs3761548) might be involved in cancer progression like gastric cancer through influencing Tregs function and the secretion of immunomodulatory cytokines such as IL-10 , IL-35 , and TGF-β . Normal tissue integrity
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2016-459: The production of the cytokine GM-CSF which is correlated to neuroinflammation. Detailed mechanisms on this front are yet to be elucidated. IL-1β has also been observed in elevated levels of the cerebrospinal fluid and brain tissues of Alzheimer patients. The amyloid-β plaques , that are characteristic of Alzheimer disease, are damage-associated molecular patterns (DAMPs) that are recognized by pattern recognition receptors (PRRs) and lead to
2064-472: The secretion of the RANK / RANKL inhibitor osteoprotegerin . Higher osteoprotegerin and IL-1β levels are a characteristic of breast cancer cells with a higher metastatic potential. The human immunodeficiency virus (HIV) infects cells of the immune system, such as macrophages, dendritic cells, and CD4 T helper cells ( T H ). The latter can be infected by the virus in various ways with different fates depending on
2112-457: The site of inflammation where they get infected again. The results is the depletion of T helper cells. Even though, levels of IL-1β in blood are not majorly different between HIV positive and negative individuals, studies have shown elevated levels of IL-1β of lymphatic tissue in HIV-infected individuals. In fact, the gut-associated lymphoid tissue ( GALT ) has a high density of immune cells as
2160-476: The state of activation of the T helper cell. Firstly, T H cells can die of viral lysis due to an active infection that produces enough virions to kill the cell . Secondly, CD4 T cells can be infected by the virus but instead of producing more viral particles, the cell enters a latent phase. In this period, the T helper cells looks identical from the outside but any stressor could lead to the renewed production of HIV and its propagation to new immune cells. Lastly,
2208-419: The terminology ) . Cytokines are produced by a broad range of cells, including immune cells like macrophages , B lymphocytes , T lymphocytes and mast cells , as well as endothelial cells , fibroblasts , and various stromal cells ; a given cytokine may be produced by more than one type of cell. They act through cell surface receptors and are especially important in the immune system ; cytokines modulate
2256-462: Was identified simultaneously in 1966 by John David and Barry Bloom. In 1969, Dudley Dumonde proposed the term "lymphokine" to describe proteins secreted from lymphocytes and later, proteins derived from macrophages and monocytes in culture were called "monokines". In 1974, pathologist Stanley Cohen, M.D. (not to be confused with the Nobel laureate named Stanley Cohen, who was a PhD biochemist; nor with
2304-435: Was the same molecule that was described by Igal Gery in 1972. He named it lymphocyte-activating factor (LAF) because it was a lymphocyte mitogen . It was not until 1984 that interleukin 1 was discovered to consist of two distinct proteins, now called interleukin-1 alpha and interleukin-1 beta. IL-1β is a member of the interleukin 1 family of cytokines . This cytokine is produced by activated macrophages , monocytes , and
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