UMLS:C0020672 - FACTA Search

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Query: UMLS:C0020672 (hypothermia)
17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of recombinant murine tumor necrosis factor (TNF) to mice results in lethal shock, characterized by hypotension, hypothermia, and dramatic induction of cytokines released in the circulation, such as interleukin-6 (IL-6). The sensitivity of mice to the effects of murine TNF varies from strain to strain. DBA/2 mice were found to be considerably more resistant to TNF than C57BL/6 mice. The resistance proved to be dominant since (C57BL/6 x DBA/2)F1 mice were also resistant. Using BXD recombinant inbred mice and a dose of TNF lethal for C57BL/6 but not for DBA/2 mice, we found that the resistance to TNF links to loci coding for corticosteroid-binding globulin (Cbg), alpha1-protease inhibitor (Spi1), contrapsin (Spi2) and the contrapsin-regulating gene Spi2r that form a gene cluster on chromosome 12. Quantitative trait-loci analysis of TNF-induced induction of IL-6 and of hypothermia also points to the importance of this locus (P < 0.0002 and P = 0.017, respectively), more particularly the Cbg and Spi2 loci, in the resistance to TNF. We propose to name the locus "TNF protection locus." The data suggest that endogenous protease inhibitors and/or glucocorticoids play a significant role in the attenuation of TNF-induced lethal shock. This study also demonstrates that loci affecting important biological responses can be identified with very high resolution using recombinant inbred mice.
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PMID:Identification of a locus on distal mouse chromosome 12 that controls resistance to tumor necrosis factor-induced lethal shock. 1004 82

Retrograde cerebral perfusion (RCP) has recently been reported to be useful for the repair of aortic arch aneurysms. However, there is a possibility that RCP supplies a limited amount of blood to the brain [1] and ischemia-reperfusion injury may occur after RCP. FR167653 (FR) is characterized as a potent suppressant of interleukin-1beta and tumor necrosis factor-alpha. We investigated the role of FR in preventing cerebral ischemia-reperfusion injury after RCP in a canine model. A total of 12 mongrel dogs was divided into two groups: in the FR group (n = 6), FR167653 (1 mg/kg/hour) was continuously administered during the period of RCP and rewarming; in the control group (n = 6), a physiological saline solution was administered at the same dosage as the FR167653 during the same period. Following hypothermia (20 degrees C) using cardiopulmonary bypass and circulatory arrest, RCP was performed by infusing oxygenated blood via the bilateral internal maxillary veins for 60 minutes at a perfusion pressure of 25 mmHg. The cerebral blood flow (CBF), cerebral metabolic rate for glucose (CMRGlu) and oxygen (CMRO2), and excretion of carbon dioxide (ExCO2) were measured. These results were expressed as the percentage of change from baseline values established immediately after anesthesia. CBF was significantly (p < 0.05) higher in the FR group than in the control group at 40 (159 +/- 25% and 82 +/- 21%, respectively) and 60 minutes (177 +/- 30% and 83 +/- 14%, respectively) after RCP. The lactate/pyruvate ratio of blood returned from the brain tissues was significantly (p < 0.05) lower in the FR group than in the control group at 40 and 60 minutes after RCP. CMRGlu was significantly (p < 0.05) higher in the FR group than in the control group 60 minutes after RCP. There was no significant difference in CMRO2 and ExCO2 between the two groups. It is concluded that FR167653 appears to be effective in protecting the brain from ischemia-reperfusion injury after RCP.http://link.springer-ny.com/link/service/journals/00547/bibs/8n3p143.html
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PMID:The Effect of FR167653 on Cerebral Ischemia-Reperfusion Injury After Retrograde Cerebral Perfusion in a Canine Model. 1038 20

Oral exposure to chlorpyrifos (CHP) in the rat results in an initial hypothermic response followed by a delayed fever. Fever from infection is mediated by the release of cytokines, including interleukin-6 (IL-6) and tumor necrosis factor (TNF alpha). This study determined if the CHP-induced fever involves cytokine-mediated mechanisms similar to that of infectious fevers. Long-Evans rats were gavaged with the corn oil vehicle or CHP (10-50 mg/kg). The rats were euthanized and blood collected at various times that corresponded with the hypothermic and febrile effects of CHP. Plasma IL-6, TNF alpha, cholinesterase activity (ChE), total iron, unsaturated iron binding capacity (UIBC), and zinc were measured. ChE activity was reduced by approximately 50% 4 h after CHP. There was no effect of CHP on IL-6 when measured during the period of CHP-induced hypothermia or fever. TNF alpha levels nearly doubled in female rats 48 h after 25 mg/kg CHP. The changes in plasma cytokine levels following CHP were relatively small when compared to > 1000-fold increase in IL-6 and > 10-fold rise in TNF alpha following lipopolysaccharide (E. coli; 50 microg/kg; i.p.)-induced fever. This does not preclude a role of cytokines in CHP-induced fever. Nonetheless, the data suggest that the delayed fever from CHP is unique, involving mechanisms other than TNF alpha and IL-6 release into the circulation characteristic of infectious fevers.
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PMID:Are circulating cytokines interleukin-6 and tumor necrosis factor alpha involved in chlorpyrifos-induced fever? 1041 84

Chlorpyrifos (CHP), an OP-based pesticide, induces hypothermia in the rat followed by a fever that persists for several days. The cytokine, tumor necrosis factor-alpha (TNF), is induced by lipopolysaccharide (LPS) and released during fever and has both pyrogenic and cryogenic (i.e. antipyretic) properties. Administering antibodies to TNF (anti-TNF) is known to disrupt fever from infection. Thus, the purpose of this study was to examine whether anti-TNF also disrupts CHP-induced changes in body temperature of the female Long-Evans rat. A positive effect would suggest a role of TNF in the etiology of OP toxicity. In study one, rats were given either saline or anti-TNF (50,000 units, i.p.). Three hours later, animals were given corn oil (CO) or 25 mg/kg CHP by oral gavage in the morning. In study two, rats were given anti-TNF followed by CO or 10 mg/kg CHP in the afternoon. Core temperature and motor activity were monitored continuously by telemetry. In study one, anti-TNF (50,000 units) had no effect on the hypothermic response to 25 mg/kg CHP. However, anti-TNF treated animals maintained higher fevers 3 days (48-96 h post-injection) after CHP treatment. In study two, anti-TNF attenuated the hypothermic response induced by 10 mg/kg CHP but had no effect on the magnitude of the delayed fever. Overall, 25 mg/kg CHP elicited a longer period of hypothermia and delayed fever compared to 10 mg/kg CHP. Anti-TNF pretreatment attenuated the hypothermic response at the lower CHP dose and exacerbated the fever at the higher CHP dose. Anti-TNF also attenuated the hypothermic effect of high doses of LPS and exacerbated LPS-induced fever. These data indicate that endogenously produced TNF is involved in the etiology of CHP mediated hypothermia and fever.
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PMID:Tumor necrosis factor is involved in chlorpyrifos--induced changes in core temperature in the female rat. 1051 30

We investigated inflammatory and physiologic parameters in sepsis models of increasing lethality induced by cecal ligation and puncture (CLP). Mice received imipenem for antibiotic therapy, and groups were sacrificed at 2, 4, 8, 12, 16, 20, and 24 h after CLP. The severity of sepsis increased with needle puncture size (lethality with 18-gauge puncture [18G], 100%; 21G, 50%; 25G, 5%; sham treatment, 0%). While the temperature (at 12 h) and the activity and diurnal rhythm (at day 4) of the 25G-treated CLP group recovered to normal, the 21G and 18G treatment groups exhibited severe hypothermia along with decreased activities. A direct correlation was also observed between the severity of sepsis and cytokine (interleukin 1beta [IL-1beta], tumor necrosis factor [TNF], IL-6, and IL-10) concentrations in both the peritoneum and the plasma. There were substantially higher cytokine levels in the more severe CLP models than in the sham-treated one. Peritoneal and plasma TNF levels were always less than 40 pg/ml in all models. None of the cytokines in the septic mice peaked within the first hour, which is in contrast to the results of most endotoxin models. Chemokine (KC and macrophage inflammatory protein 2) profiles also correlated with the severity of sepsis. Except for the chemokines, levels of inflammatory mediators were always higher at the site of inflammation (peritoneum) than in the circulation. Our study demonstrated that sepsis of increasing severity induced increased cytokine levels both within the local environment (peritoneum) and systemically (plasma), which in turn correlated with morbidity and mortality.
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PMID:Immunopathologic alterations in murine models of sepsis of increasing severity. 1056 81

Changes in body temperature and cell infiltration, mediated by cytokines including tumor necrosis factor-alpha (TNF-alpha), occur during inflammation, but a role of body temperature on inflammatory responses remains obscure. Intraperitoneal injection of 10% casein to mice resulted in transient hypothermia followed by neutrophil accumulation in peritoneal cavities. Peritoneal TNF-alpha was rapidly raised, and pretreatment of mice with an anti-TNF-alpha antibody promoted temperature restoration and partially inhibited neutrophil accumulation. To investigate direct effects of body temperature on neutrophils, peritoneal or peripheral blood neutrophils were cultured at 35 degrees C or 37 degrees C with or without recombinant murine TNF-alpha (100 ng/ml) or a protein synthesis inhibitor cycloheximide (1 microg/ml). Significant inhibition of spontaneous and TNF-alpha-induced apoptosis was obtained at 35 degrees C compared with 37 degrees C, an effect that was not altered by the addition of cycloheximide. Moreover, phagocytic ability of peritoneal neutrophils was significantly enhanced by incubating them at the lower temperature. These results indicate that mild hypothermia induced by endogenous TNF-alpha has enhancing roles on neutrophil survival and function during peritoneal inflammation.
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PMID:Role of hypothermia induced by tumor necrosis factor on apoptosis and function of inflammatory neutrophils in mice. 1064 34

Patients with biliary tract obstruction have unexplained, inordinately high rates of perioperative morbidity and mortality, whereas cholestatic animals display abnormal hypothalamic responses to pyrogenic stimuli. We asked if obstructive cholestasis was associated with abnormal fever generation. Male Sprague-Dawley rats (250 g) underwent laparotomy for implantation of thermistors and either bile duct resection (BDR) or sham operation. After recovery, temperatures were recorded by telemetry and conscious, unrestrained rats in each group were injected intraperitoneally with either interleukin-1beta (IL-1beta;1 microg/kg) or Escherichia coli lipopolysaccharide (LPS; 50 microg/kg). Baseline temperatures in both groups were similar. Febrile responses after IL-1beta injection in BDR and sham groups were not significantly different. However, in response to LPS injection, BDR rats showed an initial hypothermia with a subsequently attenuated febrile response. Administration of anti-tumor necrosis factor-alpha (TNF-alpha) antibody 2 h before LPS injection blocked the LPS-induced hypothermia seen in BDR animals. However, serum levels of TNF-alpha were not significantly different between sham and BDR animals after LPS injection at any time point measured (0, 1.5, and 3 h).
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PMID:Attenuated febrile response to lipopolysaccharide in rats with biliary obstruction. 1089 60

Heat-shock proteins (HSPs) function in the cellular response to injury. Increased expression of these proteins was first described in response to hyperthermia, although their production may be prompted by a variety of metabolic insults. HSPs protect cellular proteins from degradation. The self-limited pancreatitis induced by hyperstimulation with supramaximal doses of cerulein is accompanied by increased HSP expression. It may be that HSPs serve a protective function in pancreatitis. We hypothesized that hyperthermia-induced production of HSP-70 would improve survival in a lethal murine model of necrotizing pancreatitis. Necrotizing pancreatitis was induced in two groups of 30 female Swiss Webster mice by feeding them a choline-deficient diet supplemented with 0.5 g% ethionine (CDE) for 72 hours. Immediately before initiation of the CDE diet, the core body temperatures of the mice in the experimental group were elevated to 42 degrees C for 12.5 minutes. Twenty mice from each group were killed after 24 hours. Pancreata were harvested, and pancreatic proteins were extracted from half of the pancreata. HSP-70 was assessed according to a standard Western blotting protocol. The remaining pancreata were used to make histologic comparisons. Serum interleukin 6 and tumor necrosis factor-alpha were determined by enzyme-linked immunosorbent assay (ELISA). Survival was determined by observation of the remaining mice. HSP-70 was expressed in pancreatic protein from all mice exposed to hypothermia but in none of the mice subjected to the CDE diet alone. Mortality was significantly reduced in mice pretreated with hyperthermia compared with control mice (p < 0.05). Survival in the hyperthermia group was 80%, whereas in the control group it was 30%. Hyperthermia resulted in expression of pancreatic HSP-70 in mice. Hyperthermia also reduced mortality in this lethal murine model of necrotizing pancreatitis. It is plausible that a causal relationship exists between HSP-70 production and improved survival in this model.
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PMID:Hyperthermia induces heat-shock protein expression, reduces pancreatic injury, and improves survival in necrotizing pancreatitis. 1097 4

The role of tumor necrosis factor (TNF) in the febrile and metabolic responses of rats to intraperitoneal injection of a high dose of lipopolysaccharide Injection of a high dose of lipopolysaccharide (LPS) induces a septic-shock-like state, which can be accompanied by phases of hypothermia and phases of fever. In the present study we monitored body core temperature and locomotor activity, both by remote radiotelemetry, as well as changes in food intake, body mass and water intake for 3 days after an intraperitoneal (i.p.) injection of a high dose of LPS (5 mg/kg) along with sterile 0.9% saline or a neutralizing form of the soluble tumor necrosis factor (TNF) type 1 receptor (referred to as TNF-binding protein, TNF bp). Intraperitoneal injection of LPS rapidly induced high concentrations of TNF in the plasma and peritoneal lavage fluid. TNF was undetectable in the plasma and peritoneal lavage fluid of animals co-injected with LPS and TNF bp, implying neutralization of peripheral bioactive TNF. Administration of LPS induced hypothermia by about 1.5 degrees C, which lasted for 5 h after injection. During the light-time periods of days 2 and 3 after injection, the rats developed a robust fever. Treatment with TNF bp resulted in a faster recovery from the LPS-induced hypothermia so that the rats developed a pronounced fever on the day of injection. Locomotor activity during night-time periods was suppressed in LPS-treated animals. The LPS-induced depression of night-time activity was not antagonized by co-injection of TNF bp. On day 1 after the injection of LPS, food intake reduced to virtually zero, water intake fell to about 30% of the control value and body mass dropped by 25 g (about 10% of total body mass). With the exception of body mass, these variables recovered slowly during days 2 and 3 after LPS injection, but did not reach the control values. The LPS-induced decreases in food intake, body mass and water intake were significantly attenuated by the treatment with TNF bp. These results confirm that TNF contributes significantly to the rats' responses to intraperitoneal injection of a high dose of LPS. The fact that treatment with TNF bp accelerated and improved the rats' ability to develop a febrile response supports the view that the fever is beneficial, since all other metabolic responses measured in this study were normalized more effectively in those rats that developed a faster and more pronounced increase in body temperature.
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PMID:The role of tumor necrosis factor (TNF) in the febrile and metabolic responses of rats to intraperitoneal injection of a high dose of lipopolysaccharide. 1104 60

We have shown previously that febrile range temperatures modify cytokine production by adult macrophages. In this study, we compared the effects of moderate hyperthermia and hypothermia on the kinetics of lipopolysaccharide (LPS)-induced cytokine expression in monocytes and macrophages of newborns and adults. During culture at 40 degrees C, the initial rates of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion were preserved, but the duration of secretion was shorter than the duration at 37 degrees C. TNF-alpha and IL1-beta concentrations in 24-h 40 degrees C culture supernatants were reduced 18%-50%. IL-6 concentration in 24-h 40 degrees C cultures was reduced 26%-29% in all cells except adult macrophages. At 32 degrees C, changes in early (2 h) and sustained (24 h) cytokine expression were reversed compared with those caused by hyperthermia. Culturing adult macrophages at 32 degrees C blunted early secretion of TNF-alpha and IL-6 by 69% and 65%, respectively, and increased TNF-alpha concentration at 24 h by 48% compared with levels at 37 degrees C. In adult monocytes cultured at 32 degrees C, early IL-6 and IL-1 beta secretion was decreased 64% and 51%, respectively. We speculate that the burst/suppression cytokine profile at febrile temperatures might enhance early activation of host defenses and prevent prolonged exposure to potentially cytotoxic cytokines. Hypothermia, on the other hand, may worsen outcome in infections by delaying and prolonging cytokine production.
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PMID:Effects of hypothermia and hyperthermia on cytokine production by cultured human mononuclear phagocytes from adults and newborns. 1115 70

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