Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules ) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related proteins.
119-474: 4O9H , 1ALU , 1IL6 , 1P9M , 2IL6 , 4CNI , 4J4L , 4NI7 , 4NI9 , 4ZS7 3569 16193 ENSG00000136244 ENSMUSG00000025746 P05231 P08505 NM_000600 NM_001318095 NM_001371096 NM_031168 NM_001314054 NP_000591 NP_001305024 NP_001358025 NP_001300983 NP_112445 Interleukin 6 ( IL-6 ) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine . In humans, it
238-422: A myokine . IL-6 was the first myokine that was found to be secreted into the blood stream in response to muscle contractions. Aerobic exercise provokes a systemic cytokine response, including, for example, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10. IL-6 was serendipitously discovered as a myokine because of the observation that it increased in an exponential fashion proportional to the length of exercise and
357-528: A certain gene polymorphism in IL-6 also appear to be more susceptible to developing encephalitis. IL-6 has been shown to lead to several neurological diseases through its impact on epigenetic modification within the brain. IL-6 activates the Phosphoinositide 3-kinase (PI3K) pathway, and a downstream target of this pathway is the protein kinase B (PKB) (Hodge et al., 2007). IL-6 activated PKB can phosphorylate
476-419: A compact, globular fold (similar to other interleukins), stabilised by the two disulphide bonds. One half of the structure is dominated by a 4-alpha-helix bundle with a left-handed twist; the helices are anti-parallel, with two overhand connections, which fall into a double-stranded anti-parallel beta-sheet. The fourth alpha-helix is important to the biological activity of the molecule. Interleukin 7 (IL-7)
595-443: A constant level. To regulate body temperature, an organism may need to prevent heat gains in arid environments. Evaporation of water, either across respiratory surfaces or across the skin in those animals possessing sweat glands , helps in cooling body temperature to within the organism's tolerance range. Animals with a body covered by fur have limited ability to sweat, relying heavily on panting to increase evaporation of water across
714-403: A constant temperature throughout the year, like the tropics or the ocean, has enabled ectotherms to develop behavioral mechanisms that respond to external temperatures, such as sun-bathing to increase body temperature, or seeking the cover of shade to lower body temperature. To cope with low temperatures, some fish have developed the ability to remain functional even when the water temperature
833-621: A feedback system to trigger these adaptations to regulate temperature accordingly. The main features of this system are stimulus, receptor, modulator, effector and then the feedback of the newly adjusted temperature to the stimulus. This cyclical process aids in homeostasis. Homeothermy and poikilothermy refer to how stable an organism's deep-body temperature is. Most endothermic organisms are homeothermic, like mammals . However, animals with facultative endothermy are often poikilothermic, meaning their temperature can vary considerably. Most fish are ectotherms, as most of their heat comes from
952-710: A further increase in non-survivors. In these patients, IL-6 was a predictor of short-term (28- and 90-day) mortality. The first FDA approved anti-IL-6 treatment was for rheumatoid arthritis. Anti-IL-6 therapy was initially developed for treatment of autoimmune diseases , but due to the role of IL-6 in chronic inflammation, IL-6 blockade was also evaluated for cancer treatment. IL-6 was seen to have roles in tumor microenvironment regulation, production of breast cancer stem cell-like cells, metastasis through down-regulation of E-cadherin, and alteration of DNA methylation in oral cancer. Advanced/ metastatic cancer patients have higher levels of IL-6 in their blood. One example of this
1071-448: A genetic change in body temperature on longevity is difficult to study in humans. There are limits both of heat and cold that an endothermic animal can bear and other far wider limits that an ectothermic animal may endure and yet live. The effect of too extreme a cold is to decrease metabolism , and hence to lessen the production of heat. Both catabolic and anabolic pathways share in this metabolic depression, and, though less energy
1190-401: A good insulator. Mammalian skin is much thicker than that of birds and often has a continuous layer of insulating fat beneath the dermis. In marine mammals, such as whales, or animals that live in very cold regions, such as the polar bears, this is called blubber . Dense coats found in desert endotherms also aid in preventing heat gain such as in the case of the camels. A cold weather strategy
1309-588: A growth factor and antibody production stimulant. The protein is secreted as a single glycosylated polypeptide, and cleavage of a signal sequence is required for its activity. Solution NMR suggests that the structure of IL2 comprises a bundle of 4 helices (termed A-D), flanked by 2 shorter helices and several poorly defined loops. Residues in helix A, and in the loop region between helices A and B, are important for receptor binding. Secondary structure analysis has suggested similarity to IL4 and granulocyte-macrophage colony stimulating factor (GMCSF). Interleukin 3 (IL3)
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#17328807948901428-503: A key role in inflammation of many autoimmune diseases, such as RA, allergies, asthma, psoriasis, and more, but it also plays a key role in the pathogenesis of these diseases. Additionally, some studies have found that IL-17 plays a role in tumorigenesis (initial formation of a tumor) and transplant rejection. The IL-17 family is thought to represent a distinct signaling system that appears to have been highly conserved across vertebrate evolution. Body temperature Thermoregulation
1547-473: A lifestyle of scavenging for short durations during the hottest hours of the day, in excess of 50 °C (122 °F), for the carcasses of insects and other forms of life which have died from heat stress. In April 2014, the South Californian mite Paratarsotomus macropalpis has been recorded as the world's fastest land animal relative to body length, at a speed of 322 body lengths per second. Besides
1666-670: A marked anti-obesity effect. IL-6 is also considered a myokine , a cytokine produced from muscle, which is elevated in response to muscle contraction. It is significantly elevated with exercise, and precedes the appearance of other cytokines in the circulation. During exercise, it is thought to act in a hormone-like manner to mobilize extracellular substrates and/or augment substrate delivery. Like in humans, there seems to be an increase in IL-6 expression in working muscle and plasma IL-6 concentration during exercise in rodents. Studies in mice with IL-6 gene knockout indicate that lack of IL-6 in mice affect exercise function. It has been shown that
1785-462: A matter of fact, eccentric exercise may result in a delayed peak and a much slower decrease of plasma IL-6 during recovery. Recent work has shown that both upstream and downstream signalling pathways for IL-6 differ markedly between myocytes and macrophages. It appears that unlike IL-6 signalling in macrophages, which is dependent upon activation of the NFκB signalling pathway, intramuscular IL-6 expression
1904-437: A more environmentally favorable location. They may do this in the morning only by raising their head from its burrow and then exposing their entire body. By basking in the sun, the lizard absorbs solar heat. It may also absorb heat by conduction from heated rocks that have stored radiant solar energy. To lower their temperature, lizards exhibit varied behaviors. Sand seas, or ergs , produce up to 57.7 °C (135.9 °F), and
2023-439: A proinflammatory cytokine. Therefore, it was first thought that the exercise-induced IL-6 response was related to muscle damage. However, it has become evident that eccentric exercise is not associated with a larger increase in plasma IL-6 than exercise involving concentric "nondamaging" muscle contractions. This finding clearly demonstrates that muscle damage is not required to provoke an increase in plasma IL-6 during exercise. As
2142-512: A recent study has shown that IL-9 is, in fact, much closer to both IL-2 and IL-15, than to IL-7. Moreover, the study showed irreconcilable structural differences between IL-7 and all the remaining cytokines signalling through the γc receptor ( IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21). Interleukin 10 (IL-10) is a protein that inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF, and GM-CSF produced by activated macrophages and by helper T cells. In structure, IL-10
2261-739: A wide variety of body cells. The term was coined by Dr Vern Paetkau, University of Victoria . Some interleukins are classified as lymphokines , lymphocyte-produced cytokines that mediate immune responses. Interleukin 1 alpha and interleukin 1 beta ( IL1 alpha and IL1 beta ) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis. Two types of IL-1 receptor, each with three extracellular immunoglobulin (Ig)-like domains, limited sequence similarity (28%) and different pharmacological characteristics have been cloned from mouse and human cell lines: these have been termed type I and type II receptors. The receptors both exist in transmembrane (TM) and soluble forms:
2380-441: Is pancreatic cancer , with noted elevation of IL-6 present in patients correlating with poor survival rates. High IL-6 levels are associated with the development of encephalitis in children and immunodeficient mouse models infected with Enterovirus 71 ; this highly contagious virus normally causes a milder illness called Hand, foot, and mouth disease but can cause life-threatening encephalitis in some cases. EV71 patients with
2499-485: Is 0.3–0.6 °C (0.5–1.1 °F) lower than oral temperature. The average difference between oral and axillary temperatures of Indian children aged 6–12 was found to be only 0.1 °C (standard deviation 0.2 °C), and the mean difference in Maltese children aged 4–14 between oral and axillary temperature was 0.56 °C, while the mean difference between rectal and axillary temperature for children under 4 years old
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#17328807948902618-470: Is a cytokine that regulates hematopoiesis by controlling the production, differentiation and function of granulocytes and macrophages. The protein, which exists in vivo as a monomer, is produced in activated T cells and mast cells, and is activated by the cleavage of an N-terminal signal sequence. IL3 is produced by T lymphocytes and T-cell lymphomas only after stimulation with antigens, mitogens, or chemical activators such as phorbol esters. However, IL3
2737-458: Is a cytokine that serves as a growth factor for early lymphoid cells of both B- and T-cell lineages. Interleukin 8 is a chemokine produced by macrophages and other cell types such as epithelial cells , airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies . In humans, the interleukin-8 protein is encoded by
2856-418: Is a homodimer. The fold contains an anti-parallel 4-alpha-helix bundle with a left handed twist, connected by a 2-stranded anti-parallel beta-sheet. The monomers are held together by 2 interchain disulphide bonds. Interleukin 6 (IL6), also referred to as B-cell stimulatory factor-2 (BSF-2) and interferon beta-2, is a cytokine involved in a wide variety of biological functions. It plays an essential role in
2975-575: Is a protein of about 160 amino acids that contains four conserved cysteines involved in disulphide bonds. IL-10 is highly similar to the Human herpesvirus 4 (Epstein-Barr virus) BCRF1 protein, which inhibits the synthesis of gamma-interferon and to Equid herpesvirus 2 (Equine herpesvirus 2) protein E7. It is also similar, but to a lesser degree, with human protein mda-7. a protein that has antiproliferative properties in human melanoma cells. Mda-7 contains only two of
3094-473: Is a well-known pleiotropic molecule, it plays a dual role in the pathogenesis of liver diseases. While it is necessary for promoting liver regeneration , IL-6 is also a highly recognized marker of systemic inflammation and its association with mortality in liver diseases has been reported by multiple studies. In patients with severe alcohol-associated hepatitis , IL-6 showed the most robust elevation among inflammatory cytokines compared to healthy controls with
3213-666: Is able to thermoregulate and keep itself at the optimum temperature for development. Koalas also can behaviorally thermoregulate by seeking out cooler portions of trees on hot days. They preferentially wrap themselves around the coolest portions of trees, typically near the bottom, to increase their passive radiation of internal body heat. To cope with limited food resources and low temperatures, some mammals hibernate during cold periods. To remain in "stasis" for long periods, these animals build up brown fat reserves and slow all body functions. True hibernators (e.g., groundhogs) keep their body temperatures low throughout hibernation whereas
3332-422: Is also an integral part of a reptile's life, specifically lizards such as Microlophus occipitalis and Ctenophorus decresii who must change microhabitats to keep a constant body temperature. By moving to cooler areas when it is too hot and to warmer areas when it is cold, they can thermoregulate their temperature to stay within their necessary bounds. Thermogenesis occurs in the flowers of many plants in
3451-434: Is also profoundly affected by hyperthermia and delirium , and convulsions may set in. Consciousness may also be lost, propelling the person into a comatose condition. These changes can sometimes also be observed in patients experiencing an acute fever . Mammalian muscle becomes rigid with heat rigor at about 50 °C, with the sudden rigidity of the whole body rendering life impossible. H.M. Vernon performed work on
3570-436: Is an illness that could happen if one is exposed to high temperatures, resulting in some symptoms such as dizziness, fainting, or a rapid heartbeat. For humans, adaptation to varying climatic conditions includes both physiological mechanisms resulting from evolution and behavioural mechanisms resulting from conscious cultural adaptations. The physiological control of the body's core temperature takes place primarily through
3689-418: Is an important mediator of fever and of the acute phase response . IL-6 is responsible for stimulating acute phase protein synthesis, as well as the production of neutrophils in the bone marrow . It supports the growth of B cells and is antagonistic to regulatory T cells . It is capable of crossing the blood–brain barrier and initiating synthesis of PGE 2 in the hypothalamus , thereby changing
Interleukin 6 - Misplaced Pages Continue
3808-667: Is an interest in developing anti-IL-6 agents as therapy against many of these diseases. The first such is tocilizumab , which has been approved for rheumatoid arthritis , Castleman's disease and systemic juvenile idiopathic arthritis . Others are in clinical trials. It has been observed that genetic inactivation of ZCCHC 6 suppresses IL‐6 expression and reduces the severity of experimental osteoarthritis in Mice. Some plant derived small molecule such as Butein have been reported to inhibit IL-6 expression in IL-1β stimulated human chondrocytes. Since IL-6
3927-457: Is below freezing; some use natural antifreeze or antifreeze proteins to resist ice crystal formation in their tissues. Amphibians and reptiles cope with heat gain by evaporative cooling and behavioral adaptations. An example of behavioral adaptation is that of a lizard lying in the sun on a hot rock in order to heat through radiation and conduction. An endotherm is an animal that regulates its own body temperature, typically by keeping it at
4046-508: Is commonly found in the senescence-associated secretory phenotype (SASP) factors secreted by senescent cells (a toxic cell-type that increases with aging ). Cancer (a disease that increases with age) invasiveness is promoted primarily though the actions of the SASP factors metalloproteinase , chemokine , IL-6, and interleukin 8 (IL-8). IL-6 and IL-8 are the most conserved and robust features of SASP. Myelodysplastic Syndromes IL-6 receptor
4165-596: Is considerable functional overlap and interaction between Substance P (SP), the natural ligand for the neurokinin type 1 receptor (NK1R, a mediator of immunomodulatory activity) and IL-6. IL-6 stimulates the inflammatory and auto-immune processes in many diseases such as multiple sclerosis , neuromyelitis optica spectrum disorder (NMOSD), diabetes , atherosclerosis , gastric cancer , depression , Alzheimer's disease , systemic lupus erythematosus , multiple myeloma , prostate cancer , Behçet's disease , rheumatoid arthritis , and intracerebral hemorrhage. Hence, there
4284-575: Is constitutively expressed in the myelomonocytic leukaemia cell line WEHI-3B. It is thought that the genetic change of the cell line to constitutive production of IL3 is the key event in development of this leukaemia. Interleukin 4 (IL4) is produced by CD4 T cells specialized in providing help to B cells to proliferate and to undergo class switch recombination and somatic hypermutation. Th2 cells, through production of IL-4, have an important function in B-cell responses that involve class switch recombination to
4403-569: Is encoded by the IL6 gene . In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine . IL-6's role as an anti-inflammatory myokine is mediated through its inhibitory effects on TNF-alpha and IL-1 and its activation of IL-1ra and IL-10 . There is some early evidence that IL-6 can be used as an inflammatory marker for severe COVID-19 infection with poor prognosis, in
4522-557: Is generated by the proteolytic cleavage of an inactive precursor molecule. A complementary DNA encoding protease that carries out this cleavage has been cloned. Recombinant expression enables cells to process precursor Interleukin 1 Beta to the mature form of the enzyme. Interleukin 1 also plays a role in the central nervous system . Research indicates that mice with a genetic deletion of the type I IL-1 receptor display markedly impaired hippocampal-dependent memory functioning and long-term potentiation , although memories that do not depend on
4641-464: Is important to identify the parts of the body that most closely reflect the temperature of the internal organs . Also, for such results to be comparable, the measurements must be conducted under comparable conditions. The rectum has traditionally been considered to reflect most accurately the temperature of internal parts, or in some cases of sex or species, the vagina , uterus or bladder . Some animals undergo one of various forms of dormancy where
4760-439: Is known as hypothermia . It results when the homeostatic control mechanisms of heat within the body malfunction, causing the body to lose heat faster than producing it. Normal body temperature is around 37°C (98.6°F), and hypothermia sets in when the core body temperature gets lower than 35 °C (95 °F). Usually caused by prolonged exposure to cold temperatures, hypothermia is usually treated by methods that attempt to raise
4879-535: Is mediated by IL-6 and its effect on epigenetic regulation of BDNF. Additional preclinical and clinical data, suggest that Substance P [SP] and IL-6 may act in concert to promote major depression. SP, a hybrid neurotransmitter-cytokine, is co-transmitted with BDNF through paleo-spinothalamic circuitry from the periphery with collaterals into key areas of the limbic system. However, both IL6 and SP mitigate expression of BDNF in brain regions associated with negative affect and memory. SP and IL6 both relax tight junctions of
Interleukin 6 - Misplaced Pages Continue
4998-479: Is observed, particularly amongst juveniles, in endotherms such as bats and birds (such as the mousebird and emperor penguin ). This allows the individuals to increase their thermal inertia (as with gigantothermy ) and so reduce heat loss. Some ectotherms share burrows of ectotherms. Other animals exploit termite mounds. Some animals living in cold environments maintain their body temperature by preventing heat loss. Their fur grows more densely to increase
5117-467: Is of key interest as: 1) a meta-analysis indicates an association of major depressive disorder, C-reactive protein and IL6 plasma concentrations, 2) NK1R antagonists [five molecules] studied by 3 independent groups in over 2000 patients from 1998 to 2013 validate the mechanism as dose-related, fully effective antidepressant, with a unique safety profile. (see Summary of NK1RAs in Major Depression) , 3)
5236-460: Is produced by adipocytes and is thought to be a reason why obese individuals have higher endogenous levels of CRP . IL-6 may exert a tonic suppression of body fat in mature mice, given that IL-6 gene knockout causes mature onset obesity. Moreover, IL-6 can suppress body fat mass via effects at the level of the CNS. The antiobesity effect of IL-6 in rodents is exerted at the level of the brain, presumably
5355-561: Is regulated by a network of signalling cascades, including the Ca / NFAT and glycogen/ p38 MAPK pathways. Thus, when IL-6 is signalling in monocytes or macrophages, it creates a pro-inflammatory response, whereas IL-6 activation and signalling in muscle is totally independent of a preceding TNF-response or NFκB activation, and is anti-inflammatory. IL-6, among an increasing number of other recently identified myokines, thus remains an important topic in myokine research. It appears in muscle tissue and in
5474-405: Is separate from the sensation of temperature . In cold environments, birds and mammals employ the following adaptations and strategies to minimize heat loss: In warm environments, birds and mammals employ the following adaptations and strategies to maximize heat loss: In humans As in other mammals, thermoregulation is an important aspect of human homeostasis . Most body heat is generated in
5593-600: Is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature as its own body temperature, thus avoiding the need for internal thermoregulation. The internal thermoregulation process is one aspect of homeostasis : a state of dynamic stability in an organism's internal conditions, maintained far from thermal equilibrium with its environment (the study of such processes in zoology has been called physiological ecology ). If
5712-414: Is the common signal transducer for several cytokines including leukemia inhibitory factor (LIF), ciliary neurotropic factor , oncostatin M , IL-11 and cardiotrophin-1 , and is almost ubiquitously expressed in most tissues. In contrast, the expression of CD126 is restricted to certain tissues. As IL-6 interacts with its receptor, it triggers the gp130 and IL-6R proteins to form a complex, thus activating
5831-876: Is to provide protection against cold temperature. For example, the skunk cabbage is not frost-resistant, yet it begins to grow and flower when there is still snow on the ground. Another theory is that thermogenicity helps attract pollinators, which is borne out by observations that heat production is accompanied by the arrival of beetles or flies. Some plants are known to protect themselves against colder temperatures using antifreeze proteins . This occurs in wheat ( Triticum aestivum), potatoes ( Solanum tuberosum ) and several other angiosperm species. Animals other than humans regulate and maintain their body temperature with physiological adjustments and behavior. Desert lizards are ectotherms, and therefore are unable to regulate their internal temperature themselves. To regulate their internal temperature, many lizards relocate themselves to
5950-481: Is to temporarily decrease metabolic rate, decreasing the temperature difference between the animal and the air and thereby minimizing heat loss. Furthermore, having a lower metabolic rate is less energetically expensive. Many animals survive cold frosty nights through torpor , a short-term temporary drop in body temperature. Organisms, when presented with the problem of regulating body temperature, have not only behavioural, physiological, and structural adaptations but also
6069-503: Is used up, still less energy is generated. The effects of this diminished metabolism become telling on the central nervous system first, especially the brain and those parts concerning consciousness; both heart rate and respiration rate decrease; judgment becomes impaired as drowsiness supervenes, becoming steadily deeper until the individual loses consciousness; without medical intervention, death by hypothermia quickly follows. Occasionally, however, convulsions may set in towards
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#17328807948906188-516: The CXCL8 gene . IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages. There are many receptors on the surface membrane capable of binding IL-8; the most frequently studied types are the G protein-coupled serpentine receptors CXCR1 and CXCR2 . Expression and affinity for IL-8 differs between
6307-667: The IL-6 like or gp130 utilising cytokines In addition to the membrane-bound receptor, a soluble form of IL-6R (sIL-6R) has been purified from human serum and urine. Many neuronal cells are unresponsive to stimulation by IL-6 alone, but differentiation and survival of neuronal cells can be mediated through the action of sIL-6R. The sIL-6R/IL-6 complex can stimulate neurites outgrowth and promote survival of neurons and, hence, may be important in nerve regeneration through remyelination. Interleukin-6 has been shown to interact with interleukin-6 receptor , glycoprotein 130 , and Galectin-3 . There
6426-406: The anterior cingulate cortex and several other limbic areas, such as the hippocampus . The anterior cingulate cortex is responsible for detecting incongruences between expectation and perceived experience. Altered connectivity of the anterior cingulate cortex in depression, therefore, may cause altered emotions following certain experiences, leading to depressive reactions. This altered connectivity
6545-639: The core temperature of false hibernators (e.g., bears) varies; occasionally the animal may emerge from its den for brief periods. Some bats are true hibernators and rely upon a rapid, non-shivering thermogenesis of their brown fat deposit to bring them out of hibernation. Estivation is similar to hibernation, however, it usually occurs in hot periods to allow animals to avoid high temperatures and desiccation . Both terrestrial and aquatic invertebrate and vertebrates enter into estivation. Examples include lady beetles ( Coccinellidae ), North American desert tortoises , crocodiles , salamanders , cane toads , and
6664-490: The follicular phase (which lasts from the first day of menstruation until the day of ovulation ), the average basal body temperature in women ranges from 36.45 to 36.7 °C (97.61 to 98.06 °F). Within 24 hours of ovulation, women experience an elevation of 0.15–0.45 °C (0.27–0.81 °F) due to the increased metabolic rate caused by sharply elevated levels of progesterone . The basal body temperature ranges between 36.7–37.3 °C (98.1–99.1 °F) throughout
6783-683: The luteal phase , and drops down to pre-ovulatory levels within a few days of menstruation. Women can chart this phenomenon to determine whether and when they are ovulating, so as to aid conception or contraception. Fever is a regulated elevation of the set point of core temperature in the hypothalamus , caused by circulating pyrogens produced by the immune system. To the subject, a rise in core temperature due to fever may result in feeling cold in an environment where people without fever do not. Some monks are known to practice Tummo , biofeedback meditation techniques, that allow them to raise their body temperatures substantially. The effects of such
6902-545: The sand lizard will hold its feet up in the air to cool down, seek cooler objects with which to contact, find shade, or return to its burrow. They also go to their burrows to avoid cooling when the temperature falls. Aquatic animals can also regulate their temperature behaviorally by changing their position in the thermal gradient. Sprawling prone in a cool shady spot, " splooting ," has been observed in squirrels on hot days. Animals also engage in kleptothermy in which they share or steal each other's body warmth. Kleptothermy
7021-410: The ventromedial hypothalamus (VMH) is a possible mechanism by which amylin treatment could interact with VMH leptin signaling to increase its effect on weight loss. It is assumed that interleukin 6 in the liver activates the homologue of the human longevity gene mINDY expression via binding to its IL-6-receptor, which is associated with activation of the transcription factor STAT3 (which binds to
7140-429: The water-holding frog . Daily torpor occurs in small endotherms like bats and hummingbirds , which temporarily reduces their high metabolic rates to conserve energy. Previously, average oral temperature for healthy adults had been considered 37.0 °C (98.6 °F), while normal ranges are 36.1 to 37.8 °C (97.0 to 100.0 °F). In Poland and Russia, the temperature had been measured axillarily (under
7259-527: The IL-6R, and which are unresponsive to IL-6. Studies in experimental animals indicate that IL-6 in the CNS partly mediates the suppression of food intake and body weight exerted by glucagon-like peptide-1 (GLP-1) receptor stimulation. Outside the CNS, it seems that IL-6 stimulates the production of GLP-1 in the endocrine pancreas and the gut. Amylin is another substance that can reduce body weight, and that may interact with IL-6. Amylin-induced IL-6 production in
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#17328807948907378-501: The IgG1 and IgE isotypes. Interleukin 5 (IL5), also known as eosinophil differentiation factor (EDF), is a lineage-specific cytokine for eosinophilpoiesis. It regulates eosinophil growth and activation, and thus plays an important role in diseases associated with increased levels of eosinophils, including asthma. IL5 has a similar overall fold to other cytokines (e.g., IL2, IL4 and GCSF), but while these exist as monomeric structures, IL5
7497-502: The amount of insulation . Some animals are regionally heterothermic and are able to allow their less insulated extremities to cool to temperatures much lower than their core temperature—nearly to 0 °C (32 °F). This minimizes heat loss through less insulated body parts, like the legs, feet (or hooves), and nose. Different species of Drosophila found in the Sonoran Desert will exploit different species of cacti based on
7616-453: The amount of muscle mass engaged in the exercise. It has been consistently demonstrated that the plasma concentration of IL-6 increases during muscular exercise. This increase is followed by the appearance of IL-1ra and the anti-inflammatory cytokine IL-10. In general, the cytokine response to exercise and sepsis differs with regard to TNF-α. Thus, the cytokine response to exercise is not preceded by an increase in plasma-TNF-α. Following exercise,
7735-563: The arm). 36.6 °C (97.9 °F) was considered "ideal" temperature in these countries, while normal ranges are 36.0 to 36.9 °C (96.8 to 98.4 °F). Recent studies suggest that the average temperature for healthy adults is 36.8 °C (98.2 °F) (same result in three different studies). Variations (one standard deviation ) from three other studies are: Measured temperature varies according to thermometer placement, with rectal temperature being 0.3–0.6 °C (0.5–1.1 °F) higher than oral temperature, while axillary temperature
7854-464: The basal plasma IL-6 concentration may increase up to 100-fold, but less dramatic increases are more frequent. The exercise-induced increase of plasma IL-6 occurs in an exponential manner and the peak IL-6 level is reached at the end of the exercise or shortly thereafter. It is the combination of mode, intensity, and duration of the exercise that determines the magnitude of the exercise-induced increase of plasma IL-6. IL-6 had previously been classified as
7973-419: The beetle's remarkable resilience and highlight the significance of understanding their physiology for effective management and conservation efforts. By numerous observations upon humans and other animals, John Hunter showed that the essential difference between the so-called warm-blooded and cold-blooded animals lies in observed constancy of the temperature of the former, and the observed variability of
8092-422: The binding site in the mIndy promoter) and thereby rise of citrate uptake and hepatic lipogenesis. Intranasally administered IL-6 has been shown to improve sleep-associated consolidation of emotional memories. There are indications of interactions between GLP-1 and IL-6 in several parts of the brain. One example is the parabrachial nuclei of the pons , where GLP-1 increases IL-6 levels and where IL-6 exerts
8211-491: The blood brain barrier, such that effects seen in fMRI experiments with these molecules may be a bidirectional mix of neuronal, glial, capillary, synaptic, paracrine, or endocrine-like effects. At the cellular level, SP is noted to increase expression of interleukin-6 (IL-6) through PI-3K, p42/44 and p38 MAP kinase pathways. Data suggest that nuclear translocation of NF-κB regulates IL-6 overexpression in SP-stimulated cells. This
8330-509: The body is unable to maintain a normal temperature and it increases significantly above normal, a condition known as hyperthermia occurs. Humans may also experience lethal hyperthermia when the wet bulb temperature is sustained above 35 °C (95 °F) for six hours. Work in 2022 established by experiment that a wet-bulb temperature exceeding 30.55°C caused uncompensable heat stress in young, healthy adult humans. The opposite condition, when body temperature decreases below normal levels,
8449-419: The body temperature back to a normal range. It was not until the introduction of thermometers that any exact data on the temperature of animals could be obtained. It was then found that local differences were present, since heat production and heat loss vary considerably in different parts of the body, although the circulation of the blood tends to bring about a mean temperature of the internal parts. Hence it
8568-410: The body's temperature setpoint. In muscle and fatty tissue, IL-6 stimulates energy mobilization that leads to increased body temperature . At 4 °C, both the oxygen consumption and core temperature were lower in IL-6 compared with wild-type mice, suggesting a lower cold-induced thermogenesis in IL-6 mice. In the absence of inflammation 10–35% of circulating IL-6 may come from adipose tissue. IL-6
8687-502: The brain; DNMT1 hypermethylates the BDNF promoter and reduces BDNF levels. Altered BDNF function has been implicated in depression, which is likely due to epigenetic modification following IL-6 upregulation. BDNF is a neurotrophic factor implicated in spine formation, density, and morphology on neurons. Downregulation of BDNF, therefore, may cause decreased connectivity in the brain. Depression is marked by altered connectivity, in particular between
8806-415: The circulation during exercise at levels up to one hundred times basal rates, as noted, and is seen as having a beneficial impact on health and bodily functioning when elevated in response to physical exercise . IL-6 signals through a cell-surface type I cytokine receptor complex consisting of the ligand-binding IL-6Rα chain ( CD126 ), and the signal-transducing component gp130 (also called CD130). CD130
8925-575: The combination of NK1RAs and IL6 blockers may represent a new, potentially biomarkable approach to major depression, and possibly bipolar disorder . Interleukin The function of the immune system primarily depends on interleukins, and rare deficiencies of a number of them have been described, all featuring autoimmune diseases or immune deficiency . The majority of interleukins are synthesized by CD4 helper T-lymphocytes , as well as through monocytes , macrophages , and endothelial cells. They promote
9044-549: The context of the wider coronavirus pandemic . IL-6 is secreted by macrophages in response to specific microbial molecules, referred to as pathogen -associated molecular patterns ( PAMPs ). These PAMPs bind to an important group of detection molecules of the innate immune system , called pattern recognition receptors (PRRs), including Toll-like receptors ( TLRs ). These are present on the cell surface and intracellular compartments and induce intracellular signaling cascades that give rise to inflammatory cytokine production. IL-6
9163-439: The cytotoxic function of NK cells and role in pathological Th1 responses, such as in inflammatory bowel disease and multiple sclerosis. Suppression of IL-12 activity in such diseases may have therapeutic benefit. On the other hand, administration of recombinant IL-12 may have therapeutic benefit in conditions associated with pathological Th2 responses. Interleukin 13 (IL-13) is a pleiotropic cytokine that may be important in
9282-422: The day. Sutherland Simpson and J.J. Galbraith observed that all nocturnal animals and birds – whose periods of rest and activity are naturally reversed through habit and not from outside interference – experience their highest temperature during the natural period of activity (night) and lowest during the period of rest (day). Those diurnal temperatures can be reversed by reversing their daily routine. In essence,
9401-451: The death temperature and paralysis temperature (temperature of heat rigor) of various animals. He found that species of the same class showed very similar temperature values, those from the Amphibia examined being 38.5 °C, fish 39 °C, reptiles 45 °C, and various molluscs 46 °C. Also, in the case of pelagic animals, he showed a relation between death temperature and
9520-574: The decreased GAD67 levels seen in the brains of people with schizophrenia. GAD67 may be involved in the pathology of schizophrenia through its effect on GABA levels and on neural oscillations . Neural oscillations occur when inhibitory GABAergic neurons fire synchronously and cause inhibition of a multitude of target excitatory neurons at the same time, leading to a cycle of inhibition and disinhibition. These neural oscillations are impaired in schizophrenia, and these alterations may be responsible for both positive and negative symptoms of schizophrenia. IL-6
9639-400: The deep organs, especially the liver, brain, and heart, and in contraction of skeletal muscles. Humans have been able to adapt to a great diversity of climates, including hot humid and hot arid. High temperatures pose serious stresses for the human body, placing it in great danger of injury or even death. For example, one of the most common reactions to hot temperatures is heat exhaustion, which
9758-575: The development and differentiation of T and B lymphocytes , and hematopoietic cells. Interleukin receptors on astrocytes in the hippocampus are also known to be involved in the development of spatial memories in mice. The name "interleukin" was chosen in 1979, to replace the various different names used by different research groups to designate interleukin 1 (lymphocyte activating factor, mitogenic protein, T-cell replacing factor III, B-cell activating factor, B-cell differentiation factor, and "Heidikine") and interleukin 2 (TSF, etc.). This decision
9877-475: The end, and death is caused by asphyxia . In experiments on cats performed by Sutherland Simpson and Percy T. Herring, the animals were unable to survive when rectal temperature fell below 16 °C (61 °F). At this low temperature, respiration became increasingly feeble; heart-impulse usually continued after respiration had ceased, the beats becoming very irregular, appearing to cease, then beginning again. Death appeared to be mainly due to asphyxia , and
9996-425: The fact that body temperatures often stay within the same temperature ranges as warm-blooded animals. Ectotherms are the opposite of endotherms when it comes to regulating internal temperatures. In ectotherms, the internal physiological sources of heat are of negligible importance; the biggest factor that enables them to maintain adequate body temperatures is due to environmental influences. Living in areas that maintain
10115-450: The family Araceae as well as in cycad cones. In addition, the sacred lotus ( Nelumbo nucifera ) is able to thermoregulate itself, remaining on average 20 °C (36 °F) above air temperature while flowering. Heat is produced by breaking down the starch that was stored in their roots, which requires the consumption of oxygen at a rate approaching that of a flying hummingbird . One possible explanation for plant thermoregulation
10234-429: The final differentiation of B cells into immunoglobulin-secreting cells, as well as inducing myeloma/plasmacytoma growth, nerve cell differentiation, and, in hepatocytes, acute-phase reactants. A number of other cytokines may be grouped with IL6 on the basis of sequence similarity. These include granulocyte colony-stimulating factor (GCSF) and myelomonocytic growth factor (MGF). GCSF acts in hematopoiesis by affecting
10353-450: The four cysteines of IL-10. Interleukin 11 (IL-11) is a secreted protein that stimulates megakaryocytopoiesis, initially thought to lead to an increased production of platelets (it has since been shown to be redundant to normal platelet formation), as well as activating osteoclasts, inhibiting epithelial cell proliferation and apoptosis, and inhibiting macrophage mediator production. These functions may be particularly important in mediating
10472-456: The gene to induce transcription. Increased IL-6, therefore, can hypermethylate DNA sequences and subsequently decrease gene expression through its effects on DNMT1 expression. The induction of epigenetic modification by IL-6 has been proposed as a mechanism in the pathology of schizophrenia through the hypermethylation and repression of the GAD67 promoter. This hypermethylation may potentially lead to
10591-405: The growth and differentiation of T cells and certain B cells through the release of secreted protein factors. These factors, which include interleukin 2 (IL2), are secreted by lectin- or antigen-stimulated T cells, and have various physiological effects. IL2 is a lymphokine that induces the proliferation of responsive T cells. In addition, it acts on some B cells, via receptor-specific binding, as
10710-503: The hematopoietic, osseous and mucosal protective effects of interleukin 11. Interleukin 12 (IL-12) is a disulphide-bonded heterodimer consisting of a 35kDa alpha subunit and a 40kDa beta subunit. It is involved in the stimulation and maintenance of Th1 cellular immune responses, including the normal host defence against various intracellular pathogens, such as Leishmania, Toxoplasma, Measles virus , and Human immunodeficiency virus 1 (HIV). IL-12 also has an important role in enhancing
10829-415: The hypothalamus and the hindbrain . On the other hand, enhanced central IL-6 trans-signaling may improve energy and glucose homeostasis in obesity Trans-signaling implicates that a soluble form of IL-6R (sIL-6R) comprising the extracellular portion of the receptor can bind IL-6 with a similar affinity as the membrane bound IL-6R. The complex of IL-6 and sIL-6R can bind to gp130 on cells, which do not express
10948-399: The hypothalamus through the process of negative feedback, thus maintaining a constant core temperature. There are four avenues of heat loss: evaporation, convection, conduction, and radiation. If skin temperature is greater than that of the surrounding air temperature, the body can lose heat by convection and conduction. However, if air temperature of the surroundings is greater than that of
11067-513: The hypothalamus, which assumes the role as the body's "thermostat". This organ possesses control mechanisms as well as key temperature sensors, which are connected to nerve cells called thermoreceptors. Thermoreceptors come in two subcategories; ones that respond to cold temperatures and ones that respond to warm temperatures. Scattered throughout the body in both peripheral and central nervous systems, these nerve cells are sensitive to changes in temperature and are able to provide useful information to
11186-415: The integrity of the hippocampus seem to be spared. However, when mice with this genetic deletion have wild-type neural precursor cells injected into their hippocampus and these cells are allowed to mature into astrocytes containing the interleukin-1 receptors, the mice exhibit normal hippocampal-dependent memory function, and partial restoration of long-term potentiation . T lymphocytes regulate
11305-431: The internal body temperature of an endotherm more or less independent of the temperature of the environment. Endotherms possess a larger number of mitochondria per cell than ectotherms, enabling them to generate more heat by increasing the rate at which they metabolize fats and sugars. Ectotherms use external sources of temperature to regulate their body temperatures. They are colloquially referred to as cold-blooded despite
11424-510: The moist surfaces of the lungs and the tongue and mouth. Mammals like cats, dogs and pigs, rely on panting or other means for thermal regulation and have sweat glands only in foot pads and snout. The sweat produced on pads of paws and on palms and soles mostly serves to increase friction and enhance grip. Birds also counteract overheating by gular fluttering , or rapid vibrations of the gular (throat) skin . Down feathers trap warm air acting as excellent insulators just as hair in mammals acts as
11543-489: The nuclear localization signal on DNA methyltransferase-1 (DNMT1). This phosphorylation causes movement of DNMT1 to the nucleus, where it can be transcribed. DNMT1 recruits other DNMTs, including DNMT3A and DNMT3B, which, as a complex, recruit HDAC1 . This complex adds methyl groups to CpG islands on gene promoters, repressing the chromatin structure surrounding the DNA sequence and inhibiting transcriptional machinery from accessing
11662-430: The only certain sign that it had taken place was the loss of knee-jerks. However, too high a temperature speeds up the metabolism of different tissues to such a rate that their metabolic capital is soon exhausted. Blood that is too warm produces dyspnea by exhausting the metabolic capital of the respiratory centre; heart rate is increased; the beats then become arrhythmic and eventually cease. The central nervous system
11781-474: The preliminary observation that plasma concentrations of IL6 are elevated in depressed patients with cancer, and 4) selective NK1RAs may eliminate endogenous SP stress-induced augmentation of IL-6 secretion pre-clinically. These and many other reports suggest that a clinical study of a neutralizing IL-6 biological or drug based antagonist is likely warranted in patients with major depressive disorder, with or without co-morbid chronic inflammatory based illnesses; that
11900-477: The production, differentiation, and function of two related white cell groups in the blood. MGF also acts in hematopoiesis, stimulating proliferation and colony formation of normal and transformed avian cells of the myeloid lineage. Cytokines of the IL6/GCSF/MGF family are glycoproteins of about 170 to 180 amino acid residues that contain four conserved cysteine residues involved in two disulphide bonds. They have
12019-473: The proliferation of T lymphocytes, which requires interaction of IL-15 with IL-15R alpha and components of IL-2R, including IL-2R beta and IL-2R gamma (common gamma chain, γc), but not IL-2R alpha. Interleukin 17 (IL-17) is a potent proinflammatory cytokine produced by activated memory T cells. This cytokine is characterized by its proinflammatory properties, role in recruiting neutrophils, and importance in innate and adaptive immunity. Not only does IL-17 play
12138-558: The quantity of solid constituents of the body. In higher animals, however, his experiments tend to show that there is greater variation in both the chemical and physical characteristics of the protoplasm and, hence, greater variation in the extreme temperature compatible with life. A 2022 study on the effect of heat on young people found that the critical wet-bulb temperature at which heat stress can no longer be compensated, T wb,crit , in young, healthy adults performing tasks at modest metabolic rates mimicking basic activities of daily life
12257-805: The receptor. These complexes bring together the intracellular regions of gp130 to initiate a signal transduction cascade through certain transcription factors , Janus kinases (JAKs) and Signal Transducers and Activators of Transcription ( STATs ). IL-6 is probably the best-studied of the cytokines that use gp130 , also known as IL-6 signal transducer (IL6ST), in their signalling complexes. Other cytokines that signal through receptors containing gp130 are Interleukin 11 (IL-11), Interleukin 27 (IL-27), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), leukemia inhibitory factor (LIF), oncostatin M (OSM), Kaposi's sarcoma-associated herpesvirus interleukin 6-like protein (KSHV-IL6). These cytokines are commonly referred to as
12376-619: The reduction of abdominal obesity by exercise in human adults can be reversed by the IL-6 receptor blocking antibody tocilizumab . Together with the findings that IL-6 prevents obesity, stimulates lipolysis and is released from skeletal muscle during exercise, the tocilizumab finding indicates that IL-6 is required for exercise to reduce visceral adipose tissue mass. Bone may be another organ affected by exercise induced IL-6, given that muscle-derived interleukin 6 has been reported to increase exercise capacity by signaling in osteoblasts. IL-6 has extensive anti-inflammatory functions in its role as
12495-402: The regulation of the inflammatory and immune responses. It inhibits inflammatory cytokine production and synergises with IL-2 in regulating interferon-gamma synthesis. The sequences of IL-4 and IL-13 are distantly related. Interleukin 15 (IL-15) is a cytokine that possesses a variety of biological functions, including stimulation and maintenance of cellular immune responses. IL-15 stimulates
12614-530: The same 12-stranded beta-sheet structure as both the heparin binding growth factors and the Kunitz-type soybean trypsin inhibitors. The beta-sheets are arranged in 4 similar lobes around a central axis, 8 strands forming an anti-parallel beta-barrel. Several regions, especially the loop between strands 4 and 5, have been implicated in receptor binding. Molecular cloning of the Interleukin 1 Beta converting enzyme
12733-528: The skin, the body gains heat by convection and conduction. In such conditions, the only means by which the body can rid itself of heat is by evaporation. So, when the surrounding temperature is higher than the skin temperature, anything that prevents adequate evaporation will cause the internal body temperature to rise. During intense physical activity (e.g. sports), evaporation becomes the main avenue of heat loss. Humidity affects thermoregulation by limiting sweat evaporation and thus heat loss. Thermoregulation
12852-472: The soluble IL-1 receptor is thought to be post-translationally derived from cleavage of the extracellular portion of the membrane receptors. Both IL-1 receptors ( CD121a/IL1R1 , CD121b/IL1R2 ) appear to be well conserved in evolution, and map to the same chromosomal location. The receptors can both bind all three forms of IL-1 (IL-1 alpha, IL-1 beta and IL-1 receptor antagonist ). The crystal structures of IL1A and IL1B have been solved, showing them to share
12971-677: The surrounding water. However, almost all fish are poikilothermic. The physiology of the Dendroctonus micans beetle encompasses a suite of adaptations crucial for its survival and reproduction. Flight capabilities enable them to disperse and locate new host trees, while sensory organs aid in detecting environmental cues and food sources. Of particular importance is their ability to thermoregulate, ensuring optimal body temperature in fluctuating forest conditions. This physiological mechanism, coupled with thermosensation, allows them to thrive across diverse environments. Overall, these adaptations underscore
13090-410: The temperature curve of diurnal birds is similar to that of humans and other homeothermic animals, except that the maximum occurs earlier in the afternoon and the minimum earlier in the morning. Also, the curves obtained from rabbits, guinea pigs , and dogs were quite similar to those from humans. These observations indicate that body temperature is partially regulated by circadian rhythms . During
13209-438: The temperature of the latter. Almost all birds and mammals have a high temperature almost constant and independent of that of the surrounding air ( homeothermy ). Almost all other animals display a variation of body temperature, dependent on their surroundings ( poikilothermy ). Thermoregulation in both ectotherms and endotherms is controlled mainly by the preoptic area of the anterior hypothalamus . Such homeostatic control
13328-513: The thermoregulation process temporarily allows the body temperature to drop, thereby conserving energy. Examples include hibernating bears and torpor in bats . Thermoregulation in organisms runs along a spectrum from endothermy to ectothermy . Endotherms create most of their heat via metabolic processes and are colloquially referred to as warm-blooded . When the surrounding temperatures are cold, endotherms increase metabolic heat production to keep their body temperature constant, thus making
13447-463: The thermotolerance differences between species and hosts. For example, Drosophila mettleri is found in cacti like the saguaro and senita ; these two cacti remain cool by storing water. Over time, the genes selecting for higher heat tolerance were reduced in the population due to the cooler host climate the fly is able to exploit. Some flies, such as Lucilia sericata , lay their eggs en masse. The resulting group of larvae, depending on its size,
13566-485: The two receptors (CXCR1 > CXCR2). Through a chain of biochemical reactions, IL-8 is secreted and is an important mediator of the immune reaction in the innate immune system response. Interleukin 9 (IL-9) is a cytokine that supports IL-2 independent and IL-4 independent growth of helper T cells. Early studies had indicated that Interleukin 9 and 7 seem to be evolutionary related and Pfam, InterPro and PROSITE entries exist for interleukin 7/interleukin 9 family. However,
13685-501: The unusually great speed of the mites, the researchers were surprised to find the mites running at such speeds on concrete at temperatures up to 60 °C (140 °F), which is significant because this temperature is well above the lethal limit for the majority of animal species. In addition, the mites are able to stop and change direction very quickly. Spiders like Nephila pilipes exhibits active thermal regulation behavior. During high temperature sunny days, it aligns its body with
13804-444: Was 0.38 °C. In humans, a diurnal variation has been observed dependent on the periods of rest and activity, lowest at 11 p.m. to 3 a.m. and peaking at 10 a.m. to 6 p.m. Monkeys also have a well-marked and regular diurnal variation of body temperature that follows periods of rest and activity, and is not dependent on the incidence of day and night; nocturnal monkeys reach their highest body temperature at night and lowest during
13923-458: Was found upregulated in high-risk MDS patients. The inhibition of IL-6 signaling pathway can significantly ameliorate the clonogenicity of MDS hematopoietic stem and progenitor cells (HSPCs), but have undetectable effect on normal HSPCs. The epigenetic effects IL-6 have also been implicated in the pathology of depression . The effects of IL-6 on depression are mediated through the repression of brain-derived neurotrophic factor (BDNF) expression in
14042-429: Was much lower than the 35°C usually assumed, at about 30.55°C in 36–40°C humid environments, but progressively decreased in hotter, dry ambient environments. The maximum temperatures tolerated by certain thermophilic arthropods exceeds the lethal temperatures for most vertebrates. The most heat-resistant insects are three genera of desert ants recorded from three different parts of the world. The ants have developed
14161-594: Was taken during the Second International Lymphokine Workshop in Switzerland (27–31 May 1979 in Ermatingen ). The term interleukin derives from ( inter- ) "as a means of communication", and ( -leukin ) "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes". The name is something of a relic; it has since been found that interleukins are produced by
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