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)

Hypothermia is neuroprotective, possibly through suppression of microglial activation. We investigated the effects of hypothermia on lipopolysaccharide (LPS) stimulated BV-2 cells. At 37 degrees C, LPS elicited strong increases in inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2), tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), accompanied by translocation of nuclear factor-kappaB (NF-kappaB) to the nucleus. Hypothermia (33 degrees C) caused complete suppression of iNOS and NO, a partial reduction of IL-6 but did not prevent TNF-alpha production or NF-kappaB translocation. In contrast, LPS induced cyclooxygenase-2 (COX-2) to higher levels under hypothermic conditions. These results show that hypothermia selectively suppresses iNOS in microglia.
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PMID:Hypothermia suppresses inducible nitric oxide synthase and stimulates cyclooxygenase-2 in lipopolysaccharide stimulated BV-2 cells. 1257 34

In colitis, chronic and recurrent inflammation is associated with a breakdown in host defence mechanisms that leads to local and systemic infection. Whether this is due to a compromised neuroimmune response has not been studied. Our aim was to determine if colitis altered the host neuroimmune response as reflected in either body temperature rhythm or the febrile responses to lipopolysaccharide (LPS). Body temperature was monitored by telemetry from conscious, unrestrained male rats treated with trinitrobenzene sulphonic acid or saline. Twenty-six days after initial induction, colitis was reactivated. Animals were given LPS (50 microg kg-1 Escherichia coli LPS) during colitis and after reactivation. At the peak of colitis, treated rats showed a disruption of circadian body temperature rhythm, manifested as day-time fever followed by night-time hypothermia. In response to LPS, controls displayed a characteristic fever, whereas treated animals had a significantly reduced fever and low plasma levels of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). During reactivation of colitis, treated animals did not mount a fever or exhibit increased plasma levels of IL-6 and TNF-alpha after LPS. We conclude that experimental colitis is associated with a compromised neuroimmune status.
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PMID:Compromised neuroimmune status in rats with experimental colitis. 1264 19

Aging is accompanied by an altered stress response that underlies increased susceptibility of the elderly patients to physiological stress such as infection and sepsis. In the present study, we investigated the effects of aging on mortality, hypothermia, and cytokine induction in mouse models of intra-abdominal sepsis and endotoxemia. Systemic inflammation associated with either cecal ligation/puncture (CLP) or injection with bacterial endotoxin, lipopolysaccharide (LPS), resulted in a significantly elevated mortality rate in aged (24 months) compared to young (4 months) mice. The aged mice also showed profound hypothermia during these inflammatory stresses; the severity of hypothermia at the early phase of sepsis or endotoxemia could predict the mortality of individual animals. The stress-mediated induction of interleukin-1beta, interleukin-6, and interleukin-10 (IL-1beta, IL-6, and IL-10) in the circulating blood tended to be higher with aging in both CLP and LPS models, and in particular, the induction of IL-6 was significantly augmented with aging. The serum level of IL-6 showed a strong correlation with degrees of hypothermia. In the heart and lungs, the induction of mRNA for IL-6 and IL-10 was also significantly enhanced with aging. These results clearly demonstrate an age-associated increase in mortality, hypothermia, and induction of IL-6 during endotoxemia and sepsis.
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PMID:Effects of aging on mortality, hypothermia, and cytokine induction in mice with endotoxemia or sepsis. 1465 93

Opiate addicts have been shown to have a high susceptibility to bacterial infection. We investigated how treatment with morphine alters lipopolysaccharide (LPS)-induced inflammatory responses in the rat. Chronic morphine alone elevated serum endotoxin levels. Animals treated with morphine and LPS (250 microg/kg) developed hypothermia, decreased mean arterial pressure (MAP), increased plasma thrombin anti-thrombin III (TAT) complex, and approximately 67% of animals exhibited progressive intramicrovascular coagulation. Morphine also enhanced LPS-induced leukocyte-endothelial adhesion (LEA), suppressed leukocyte flux, and corticosterone production, and elevated interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6 serum levels. Our study presents both the molecular and cellular mechanisms underlying the potentiated LPS-induced inflammation and accelerated progression to septic shock seen with chronic morphine exposure.
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PMID:Chronic morphine accelerates the progression of lipopolysaccharide-induced sepsis to septic shock. 1502 69

Recent experimental data have shown that levels of matrix metalloproteinase-9 (MMP-9) increase after traumatic brain injury (TBI), degrading components of the basal lamina disrupting the blood-brain barrier. However, the post-traumatic secretion patterns of MMP-9 in humans are unknown. We measured the concentration of MMP-9 in plasma after TBI at the same time as the concentration of interleukin-6 (IL-6) in serum. Levels of MMP-9 and IL-6 in systemic arterial and jugular venous blood from seven patients with TBI were measured on days 0 and 1 post-injury. All patients underwent hypothermia at 32-35 degrees C as soon as possible after admission. Before induction of hypothermia, levels of MMP-9 in arterial and internal jugular venous blood exceeded the normal range. Higher MMP-9 levels were detected in internal jugular venous blood than in arterial blood. After hypothermia had been induced, MMP-9 levels in arterial blood and internal jugular venous blood decreased significantly, to within the normal range. In addition to these changes, a significant correlation was seen between levels of MMP-9 and IL-6 in internal jugular venous blood during the investigation period. These results indicate that MMP-9 is elevated in patients with acute TBI, and may play an important role in traumatic brain damage. The elevation of MMP-9 is associated with inflammatory events following TBI. Hypothermic intervention may suppress the elevation of MMP-9 with suppression of the inflammatory response, affording neuroprotection in TBI.
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PMID:Increased matrix metalloproteinase-9 in blood in association with activation of interleukin-6 after traumatic brain injury: influence of hypothermic therapy. 1568 62

Previous studies have suggested that interleukin-6 (IL-6) serves as both a marker and a mediator for the severity of sepsis. We tested whether interleukin 6 knockout (IL-6KO) mice were more susceptible to sepsis mortality induced by cecal ligation and puncture. IL-6KO and wild-type (WT) mice were subjected to increasing degrees of sepsis severity. Physiologic support was given with fluids and appropriate antibiotics. Plasma IL-6 levels were determined 6 h after the onset of sepsis, and a complete hematologic profile was performed on day 2. As expected, increasing sepsis severity resulted in greater and more rapid mortality. However, the mortality was nearly identical in the IL-6KO and WT mice. All WT septic mice had high plasma levels of IL-6 6 h after the onset of sepsis, while IL-6KO were near or below the lower limit of detection. Among the WT mice, mortality was significantly higher in mice with plasma IL-6 >3,000 pg/ml. Both IL-6KO and WT mice destined to die in the early stages of sepsis had substantial and nearly identical weight gain in the first 24 h. However, at later stages the WT mice had significantly greater weight loss than the KO mice. The KO mice failed to develop the characteristic hypothermia within the first 24 h of severe sepsis routinely observed in the WT mice. These data demonstrate that IL-6 serves as a marker of disease severity in sepsis and does modulate some physiologic responses, but complete lack of IL-6 does not does not alter mortality due to sepsis.
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PMID:Role of interleukin-6 in mortality from and physiologic response to sepsis. 1584 78

Our previous studies showed that beta(2)-microglobulin knockout mice treated with anti-asialoGM1 (beta2MKO/alphaAsGM1 mice) are resistant to injury caused by cecal ligation and puncture (CLP). However, CLP-induced injury is complex. Potential mechanisms of injury include systemic infection, cecal ischemia, and translocation of bacterial toxins such as endotoxin and superantigens. Currently, it is unclear which of these mechanisms of injury contributes to mortality in wild-type mice and whether beta2MKO/alphaAsGM1 mice are resistant to any particular mechanisms of injury. In the present study, we hypothesized that systemic infection is the major cause of injury after CLP in wild-type mice and that beta2MKO/alphaAsGM1 mice are resistant to infection-induced injury. To test this hypothesis, wild-type and beta2MKO/alphaAsGM1 mice were treated with the broad-spectrum antibiotic imipenem immediately after CLP to decrease the impact of systemic infection in our model. Treatment of wild-type and beta2MKO/alphaAsGM1 mice with imipenem decreased bacterial counts by at least two orders of magnitude. However, all wild-type mice, whether treated with saline or imipenem, died by 42 h after CLP and had significant hypothermia, metabolic acidosis, and high plasma concentrations of the cytokines interleukin-6, macrophage inflammatory protein-2, and keratinocyte-derived chemokine. beta2MKO/alphaAsGM1 mice showed 40% long-term survival, which was increased to 90% by imipenem treatment. beta2MKO/alphaAsGM1 mice had less hypothermia, decreased metabolic acidosis, and lower cytokine concentrations at 18 h after CLP compared with wild-type mice. These results suggest that infection is not the major cause of mortality for wild-type mice in our model of CLP. Other mechanisms of injury such as cecal ischemia or translocation of microbial toxins may be more important. beta2MKO/alphaAsGM1 mice appear resistant to these early, non-infection-related causes of CLP-induced injury but showed delayed mortality associated with bacterial dissemination, which was ablated by treatment with imipenem.
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PMID:Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient beta(2)-microgloblin knockout mice. 1616 41

Pneumolysin, the pore-forming toxin produced by Streptococcus pneumoniae, may have an application as an immunogenic carrier protein in future pneumococcal conjugate vaccines. Most of the 90 S. pneumoniae serotypes identified produce pneumolysin; therefore, this protein may confer non-serotype-specific protection against pneumococcal infections such as pneumonia, meningitis, and otitis media. However, as pneumolysin is highly toxic, a nontoxic form of pneumolysin would be a more desirable starting point in terms of vaccine production. Previous pneumolysin mutants have reduced activity but retain residual toxicity. We have found a single amino acid deletion that blocks pore formation, resulting in a form of pneumolysin that is unable to form large oligomeric ring structures. This mutant is nontoxic at concentrations greater than 1,000 times that of the native toxin. We have demonstrated that this mutant is as immunogenic as native pneumolysin without the associated effects such as production of the inflammatory mediators interleukin-6 and cytokine-induced neutrophil chemoattractant KC, damage to lung integrity, and hypothermia in mice. Vaccination with this mutant protects mice from challenge with S. pneumoniae. Incorporation of this mutant pneumolysin into current pneumococcal vaccines may increase their efficacy.
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PMID:Construction and immunological characterization of a novel nontoxic protective pneumolysin mutant for use in future pneumococcal vaccines. 1636 15

Heatstroke is a life-threatening illness characterized by an elevated core body temperature (>40 degrees C) and dysfunction of central nervous system, which results in delirium, convulsions, or coma. Despite adequate hypothermia or other care-therapy, heatstroke is often fatal. On the basis of our knowledge of the pathophysiology on heatstroke, we hypothesized that heatstroke is a form of hyperthermia associated with the acute physiological alterations, the cytotoxicity of heat, systemic inflammatory response, oxidative damage and attenuated heat-shock response leading to a syndrome of multi-organ dysfunction. In view of above-mentioned situation, the physiological factors underlying heatstroke and the corresponding possible therapeutic strategies to avert the complications of this disorder would be summarized in this review so as to provide some therapeutic guidelines for heatstroke. Heatstroke is a very complicated process. Acute physiological alterations, such as low arterial hypotension, intracranial hypertension, cerebral hypoperfusion, cerebral ischemia, and increased intracellular metabolism rate, occurred while exposed to a high ambient temperature. Hyperpyrexia caused cytotoxicity, resulting the degradation and aggregation of extensive intracellular proteins, influencing the change of membrane stability and fluidity, damaging the transmembrane transport of protein and the function of surface receptor, and inducing different cytoskeletal changes. Heatstroke resembles sepsis in many aspects, and endotoxemia and cytokines may be implicated in its pathogenesis. The concentration of interleukin-6 was positively correlated with the severity of heatstroke. The excessive accumulation of cytotoxic free radicals and oxidative damage may occur in the brain tissues during the genesis and development of heatstroke. The circulatory shock and cerebral ischemia resultant from heatstroke correlated closely with the free radicals (especially free radicals of peroxide and superoxide), the peroxidation of lipids, and low activity of antioxidase in the brain. Heat-shock proteins (Hsps) played a critical role during the process obtaining thermotolerance, therefore, protected from stress-induce cellular damage. Host factors or physiologically limiting factors, for instance, aging, existing illness, dehydration, deep insomnia, lack of acclimation to heat, inadequate physical fitness, and certain genetic polymorphisms were associated with a low level of Hsps expression and might favor the progression from heat stress to heatstroke. Some measures, such as molecular chaperonines, anti-inflammatory agents, antioxidant agents, and modulators of Hsps would be good for the patients with heatstroke.
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PMID:Pathophysiological factors underlying heatstroke. 1663 16

Brain protection is crucial during neonatal and pediatric cardiac surgery. The major methods for brain protection are the administration of steroids and deep hypothermia. Therefore, we have investigated the impact of methylprednisolone (MP) administration and deep hypothermia on neonatal mouse astrocytes, neurons and BV-2 microglia cells. Brain cells were pretreated with MP (100 mM) and incubated according to a deep hypothermia protocol mimicking temperature changes during cardiac surgery in children: deep hypothermia (2 h at 17 degrees C, phase 1), slow rewarming (2 h up to 37 degrees C, phase 2), and normothermia (20 h at 37 degrees C, phase 3). In all brain-related cell types cytotoxicity was investigated as well as the release of the pro-inflammatory cytokine interleukin-6 (IL-6), which plays a major role in neuroprotection and neuroregeneration. Deep hypothermia induces substantial cytotoxicity and the secretion of IL-6 by astrocytes, BV-2 microglia cells and neurons. MP administration has no influence on the cell survival and IL-6 release of normothermic astrocytes, BV-2 microglia cells and neurons, while hypothermia-induced cytotoxicity and IL-6 secretion are significantly suppressed by MP. These data suggest that MP increases cell survival after deep hypothermia but also suppresses important neuroprotective and regenerative processes induced by IL-6. Hence, more specific immune modulation than that provided by MP may be needed to protect the brain during neonatal and pediatric cardiac surgery.
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PMID:Methylprednisolone attenuates hypothermia- and rewarming-induced cytotoxicity and IL-6 release in isolated primary astrocytes, neurons and BV-2 microglia cells. 1686 Apr 72

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