Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor-alpha production and products of mast cell, basophil, and eosinophil degranulation (prostaglandin D2, histamine, and eosinophil cationic protein) were prospectively studied in 26 children undergoing cardiac operations. The relationship between inflammatory response to cardiopulmonary bypass and transient postoperative arrhythmias was analyzed. Cardiopulmonary bypass was conducted with circulatory arrest and deep hypothermia in 10 patients and with continuous low-flow and moderate hypothermia in 16 patients. Transient postoperative arrhythmias diagnosed on standard or atrial electrocardiograms (or both) were seen in eight of the 26 examined children: accelerated junctional rhythm (n = 3), junctional ectopic tachycardia (n = 3), second-degree atrioventricular block (n = 1), and third-degree atrioventricular block (n = 1). Children with transient postoperative arrhythmias were younger than those without (p < 0.05). Compared with baseline values, there was in all patients a significant release of histamine and eosinophil cationic protein (p < 0.05) related to cardiopulmonary bypass, reaching peak values 4 hours after the operation. In contrast, tumor necrosis factor-alpha production and prostaglandin D2 release were not significant. This suggests that activated basophils but not mast cells are the major sources of histamine liberated during and after cardiopulmonary bypass. Histamine release but not eosinophil cationic protein release correlated with circulatory arrest and deep hypothermia (p < 0.05), suggesting the participation of physicochemical alterations of circulating basophils leading to histamine liberation. Four hours after the operation, patients with transient postoperative arrhythmias had significantly higher blood concentrations of histamine (p < 0.02) and eosinophil cationic protein (p < 0.05) than did those without transient postoperative arrhythmias. On the first postoperative day, four of the eight patients with transient postoperative arrhythmias had persisting elevated histamine levels, whereas in patients without transient postoperative arrhythmias histamine reached baseline values. The multivariate analysis retained histamine release and eosinophil cationic protein variations related to cardiopulmonary bypass for the emerging model to predict transient postoperative arrhythmias. The results of this study show significant histamine release related to cardiopulmonary bypass. Furthermore, they document a possible relationship between circulating histamine and transient postoperative arrhythmias. The latter may therefore be suspected among the consequences of the inflammatory response to cardiopulmonary bypass.
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PMID:Histamine liberation related to cardiopulmonary bypass in children: possible relation to transient postoperative arrhythmias. 862 22

Lipopolysaccharide (LPS), an endotoxin, produces pain behavior, inflammation, and changes in immune function. Many of these effects are secondary to the production of cytokines. In the present study, we investigated the effect of LPS on the releasing function of afferent terminals as measured by calcitonin gene-related peptide (CGRP) release in ex vivo perfused rat trachea, and examined the possible role of the cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as intermediaries in this effect. Systemic injection of LPS (0.75 mg/kg, i.p.) in adult rats induced an increase in body temperature followed by hypothermia, indicating ongoing infection. We observed that capsaicin-induced (0.1 microM) tracheal CGRP release was significantly enhanced in the LPS-treated animals after 5 hr. This enhancement of the peptide release by LPS was blocked by IL-1beta tripeptide antagonist Lys-D-Pro-Thr (10 microM) and mimicked by IL-1beta and TNF-alpha (10-100 pg/ml), suggesting that the potentiating effect of LPS on CGRP release is mediated by generation of IL-1beta and TNF-alpha. IL-1beta-induced augmentation of CGRP release was blocked by Lys-D-Pro-Thr. Additionally, the cyclooxygenase inhibitor ketorolac (10 microM) significantly attenuated the facilitatory effects of LPS and IL-1b, indicating involvement of prostanoids. These findings suggest that endotoxin treatment generated cytokines such as IL-1b and TNF-alpha that regulated the peripheral releasing function of primary sensory afferents by sensitizing the terminals and facilitating peptide release. This effect is prostanoid dependent.
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PMID:Involvement of cytokines in lipopolysaccharide-induced facilitation of CGRP release from capsaicin-sensitive nerves in the trachea: studies with interleukin-1beta and tumor necrosis factor-alpha. 876 61

During endothelial cell activation, the formation and expression of E-selectin require transcriptional activation of the E-selectin gene, mediated by the coordinated action of several transcription factors and cis-acting elements in its 5'-flanking region. It is reported that in vitro hypothermia (25 degrees C) transiently inhibits transcriptional activation and surface expression of E-selectin as well as neutrophil adherence to cultured human umbilical vein endothelial cells (HUVECs) treated with lipopolysaccharide (LPS), interleukin-1 (IL-1), or tumor necrosis factor (TNF). Rewarming HUVECs treated with LPS, IL-1, or TNF to 37 degrees C restores E-selectin transcript accumulation, E-selectin surface expression, and neutrophil adherence to HUVECs at levels equivalent to similarly treated HUVECs maintained at 37 degrees C continuously. Despite the absence of detectable E-selectin transcription at 25 degrees C, activation of the transcription factor NF-kappaB still occurred in HUVECs treated with LPS, IL-1, or TNF, indicating that signal transduction was not blocked by hypothermia. It is concluded that neutrophil adherence to activated endothelium mediated by E-selectin is reversibly inhibited by hypothermia. The protective effect of hypothermia clinically (e.g., cardiopulmonary bypass) may, in part, be mediated by transiently inhibiting the expression of an endothelial cell activation phenotype.
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PMID:Hypothermia inhibits human E-selectin transcription. 881 30

The vascular endothelium has a number of functions that may mediate many of the ischemia-reperfusion (IR) phenomena. The gatekeeper function is disturbed and increased capillary permeability results in edema and organ dysfunction. Vasomotor function is altered, with impairment of relaxation and augmentation of constrictor responses. Coagulation becomes imbalanced, favoring the procoagulant pathways that lead to thrombosis. Vascular adhesion molecules (integrins, selectins) are upregulated or expressed to mediate the adherence and subsequent destructive effects of neutrophils as they interact with the endothelium and the underlying organs. Finally, the more chronic vascular endothelial response may be proliferation of all cellular components of the vessel wall, leading, e.g., to intimal hyperplasia or restenosis. Ultimately, the endothelium plays a significant role either in the reparative processes that lead to recovery of the organ (myocardial stunning) or in the destructive processes that lead to cell or organ death (myocardial infarction). Our research group has been interested in the selectins, particularly E-selectin (endothelial) and P-selectin (platelet). E-selectin is not constitutively present on endothelial cells but can be upregulated by inflammatory mediators such as the cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and endotoxin. We have investigated the upregulation of E-selectin with cytokines in both hypoxia and hypothermia. Hypoxia appears to enhance E-selectin upregulation on stimulation with IL-1 or TNF-alpha, although hypothermia (to 25 degrees C) blunts this response. With rewarming to 37 degrees C, the transduction and surface expression return.
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PMID:The microvascular cell and ischemia-reperfusion injury. 893 80

The systemic symptoms, tissue lesions and release of cytokines were analysed in four isogenic mouse strains with distinct haplotypes injected with various doses of Loxosceles intermedia spider venom. The estimated LD50 were 24.5 microg for C57Bl/6, 17.6 microg for BALB/c, 6.3 microg for C3H/HeJ and 4.6 microg for A/Sn mice. Prostration, acute cachexia, hypothermia, neurological disorders and hemoglobinuria were the signals preceding death. Accumulation of eosinophilic material inside the proximal and distal renal tubules and acute tubular necrosis were the most common histopathological findings. Death was prevented by previous treatment of venom with specific antivenom serum. The protein F35 purified from the whole venom retained the ability to induce the symptoms of the whole venom. The cytokines tumor necrosis factor (TNF), interleukins IL-6 and IL-10 and the radical nitric oxide were detected in serum at different levels after venom injection. These findings indicate that the state of shock produced in mice by whole endotoxin-free L. intermedia venom or by its purified fraction, protein F35, mimics the endotoxemic shock, that susceptibility to the systemic effects of the venom varies among mice of different haplotypes and that the pattern of in vivo cytokine release resembles that of endotoxemic shock.
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PMID:Endotoxemic-like shock induced by Loxosceles spider venoms: pathological changes and putative cytokine mediators. 962 May 87

Lipopolysaccharide (LPS) and homologous cytokines were tested for their effect on core temperature in mice using battery-operated telemetric devices placed in the peritoneal cavity. One microgram LPS injected intraperitoneally (i.p.) induced a biphasic effect on core body temperature (Tc), a rapid decrease in Tc with a peak around 30-45 min followed by a prolonged rise around 150-300 min. When a higher dose of LPS (5 microg) was used, the hypothermia was increased in magnitude and lasted much longer, and no fever was observed. Both the decrease and the increase in Tc caused by LPS were prevented by pretreating the mice with indomethacin, a cyclooxygenase inhibitor, but not by a nitric oxide synthase inhibitor. Mouse interleukin-1beta (mIL-1beta, 100 ng, i.p.) induced changes resembling those to LPS, a short-lived decrease in Tc, followed by a small increase. When 1 microg mIL-1beta was injected a profound hypothermia lasting more than 3 h was observed. Mouse IL-6 (1 microg) failed to alter core temperature after either intravenous (i.v.) or i.p. administration. Human IL-6 was also ineffective. Recombinant mouse tumor necrosis factor-alpha (mTNFalpha) also failed to alter the core temperature of mice when injected at a dose of 1 microg (i.p. or i.v.). However, a higher dose of mTNFalpha (5 microg i.p.) caused a short-lived decrease in Tc, followed by a small increase. Similar results were obtained with LPS and the cytokines in C57Bl/6J mice, except that mIL-1beta was ineffective in this strain. These results indicate that the endocrine, neurochemical and behavioral responses to IL-1, IL-6 and TNFalpha administration cannot be explained by changes in Tc, although they may contribute to them. They also suggest that IL-1beta may account for the fever observed following LPS, but that these cytokines are probably not the only factors involved in LPS-induced changes in Tc.
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PMID:Effect of homologous interleukin-1, interleukin-6 and tumor necrosis factor-alpha on the core body temperature of mice. 965 Aug 15

Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) have been implicated as key mediators in inflammation, morbidity, and mortality associated with sepsis. We examined the role of IL-6 and TNF-alpha signaling on hypothermia, fever, cachexia, anorexia, and survival during sepsis induced by cecal ligation and puncture (CLP) in male and female gene knockout mice. Male wild-type mice developed an initial hypothermia and subsequent fever during sepsis. Male IL-6 knockout mice did not develop fever; rather, they maintained a profound hypothermia during sepsis. Male TNF p55/p75 receptor (TNFR) knockout mice had attenuated hypothermia, but developed a virtually identical fever as wild-type mice. Cachexia did not differ between male wild-type and IL-6 or TNFR knockout mice, whereas anorexia was prolonged in IL-6 knockout mice. Due to the rapid lethality of sepsis in female mice, survival was the only variable we were able to statistically compare among female genotypes. Female wild-type mice had significantly decreased survival compared with male wild-type mice. Survival was significantly enhanced in male and female TNFR knockout mice compared with their wild-type controls. Lack of IL-6 did not affect male or female lethality. These data support the hypothesis that IL-6 is a key mediator of fever and food intake, whereas TNF is responsible for the initial hypothermia and lethality of sepsis in both sexes of mice. The enhanced lethality of CLP-treated female mice supports a role for sex steroids during sepsis.
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PMID:Role of IL-6 and TNF in thermoregulation and survival during sepsis in mice. 968 88

Lipopolysaccharides (LPS, endotoxin) of gram-negative bacteria are among the main causes of sepsis and septic shock. In the present study, the influence of temperature on the biological activity of LPS was investigated. Lowering the temperature from 37 degrees C to 34.5 degrees C or to 30 degrees C significantly enhances in vitro tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 release induced by different LPS chemotypes and heat-inactivated Escherichia coli. This cytokine-increasing effect of lowering the temperature is highly mediated by serum proteins, particularly by LPS-binding protein (LBP) and low-density lipoproteins (LDL). In contrast, cytokine production induced by the superantigen toxic shock syndrome toxin-1 (TSST-1) from Gram-positive Staphyloccoccus aureus decreases by around 70% at 30 degrees C as compared with 37 degrees C, corresponding to the expected effect of change in temperature and regardless of the presence of serum proteins. In order to explain the unexpected biological hypothermia effect with regard to LPS, the fluidity state of the lipid A portion of LPS as one important physico-chemical property possibly involved was investigated. The fluidity, determined by fluorescence polarization measurements, was found to decrease with decreasing temperature. These data suggest that a low fluid LPS chemotype is biologically more active than a more fluid one (and vice versa). Statistical analysis of the results shows a strong correlation between cytokine secretion and fluidity state of a given LPS chemotype (0.71 < r < 0.89, all P<0.01). As a clinical consequence, these data may be one possible explanation for the higher mortality rate of hypothermic Gram-negative sepsis.
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PMID:Hypothermia enhances the biological activity of lipopolysaccharide by altering its fluidity state. 976 Jan 71

The aim of the present study was to examine a possible involvement of leukotrienes (LTs) in lipopolysaccharide (LPS)-induced body temperature (Tb) response. We examined the effect of MK-886, an inhibitor of LT synthesis, on changes in Tb, plasma tumor necrosis factor-alpha (TNF-alpha), hypothalamic LT, and PGE2 production. Intraperitoneal injection of LPS (50 microgramg/mouse) led to a decrease in Tb starting 1 h after the injection. The hypothermic effect of LPS was accompanied by a significant elevation in TNF-alpha level in plasma and in LT and PGE2 production by ex vivo-incubated hypothalamus. MK-886 (1 mg/kg ip) administered 4 h before LPS efficaciously prevented LPS-induced hypothermia in mice. Pretreatment of mice with MK-886 did not alter the LPS-stimulated increase in plasma TNF-alpha. MK-886 significantly inhibited LT and enhanced PGE2 production in hypothalamus compared with LPS alone. These results suggest that 1) LPS-induced hypothermia may be mediated by LTs and 2) the antihypothermic effect of MK-886 is not associated with TNF-alpha bioactivity.
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PMID:Evidence supporting involvement of leukotrienes in LPS-induced hypothermia in mice. 988 77

Interleukin (IL)-10 inhibits the synthesis of proinflammatory cytokines implicated in fever, including IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha. We hypothesized that IL-10 functions as an antipyretic in the regulation of fevers to lipopolysaccharide (LPS) and turpentine. Body temperature was measured by biotelemetry. Swiss Webster (SW) mice treated with recombinant murine IL-10 were resistant to fever induced by a low dose of LPS (100 microgram/kg ip) and to the hypothermic and febrile effects of a high (septiclike) dose of LPS (2.5 mg/kg ip). IL-10 knockout mice developed an exacerbated and prolonged fever in response to a low dose of LPS (50 microgram/kg ip) compared with their wild-type counterparts. At 4 h after injection of the low dose of LPS, plasma levels of IL-6, but not TNF-alpha, were significantly elevated in the IL-10 knockout mice compared with their wild-type controls (ANOVA, P < 0.05). After injection of the same high dose of LPS injected into SW mice, wild-type mice developed a fever at 24 h whereas IL-10 knockout mice immediately developed a profound hypothermia that lasted through 41 h (ANOVA, P < 0.05). Body weight and food intake were more significantly depressed in response to the high dose of LPS in the knockout mice compared with their wild-type controls. Only 30% of the IL-10 knockout mice survived compared with 100% of the wild-type mice (Fisher's exact test, P < 0.05). Fever in response to the injection of turpentine (100 microliter/mouse sc) did not differ between wild-type and IL-10 knockout mice. These data support the hypotheses that 1) IL-10 functions as an endogenous antipyretic following exposure to LPS, 2) a putative mechanism of the early antipyretic action of IL-10 is through the inhibition of plasma levels of IL-6, 3) IL-10 has a protective role in the lethal effects of exposure to high levels of LPS, and 4) endogenous IL-10 does not have a role in fever induced by turpentine.
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PMID:An antipyretic role for interleukin-10 in LPS fever in mice. 988 80


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