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)

The on-going high mortality from sepsis motivates continuous research for novel therapeutic strategies. Neuropeptide Y (NPY), a sympathetic neurotransmitter, has been shown to increase survival in experimental septic shock in rats. This protective effect might be due to immunological, cardiovascular or thermoregulatory effects. The aim of this study was to examine the in vivo effect of peripherally administered NPY on body temperature, blood pressure and heart rate in endotoxaemic animals. In order to obtain clinically relevant data, various physiological parameters were monitored in parallel via radio-telemetry in chronically intravenously cannulated, freely behaving rats. Rats received a sublethal bolus of lipopolysaccharide (LPS, 100 microg kg(-1) I.V.) and the three parameters were continuously recorded for 72 h. Endotoxaemic rats showed a long-lasting hypotension, an initial hypothermia (-0.5 degrees C), followed by a prolonged febrile phase (+1.6 degrees C 6 h after endotoxin challenge) associated with a decrease of the circadian rhythm amplitude of temperature. Pretreatment with NPY (160 pmol kg(-1) I.V. over 75 min) prevented hypotension and significantly stabilized body temperature immediately following the application. The febrile phase was effectively reduced for at least 72 h. These telemetrically obtained findings clearly demonstrate that pretreatment with NPY positively influences two life-threatening symptoms in endotoxaemia and might be a future option for a successful clinical treatment regimen.
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PMID:Neuropeptide Y stabilizes body temperature and prevents hypotension in endotoxaemic rats. 1538 81

In view of the potential involvement of peripherally synthesized, circulating amphipathic mediators [such as platelet-activating factor (PAF) and prostaglandin E(2)] in the systemic inflammatory response to lipopolysaccharide (LPS), we hypothesized that transport of amphipaths by albumin is essential for conveying peripheral inflammatory signals to the brain. Our first specific aim was to test this hypothesis by studying LPS-induced fever and hypothermia in Nagase analbuminemic rats (NAR). NAR from two different colonies and normalbuminemic Sprague-Dawley rats were preimplanted with jugular catheters, and their febrile responses to a mild dose of LPS (10 microg/kg i.v.) at thermoneutrality and hypothermic responses to a high dose of LPS (500 microg/kg i.v.) in the cold were studied. NAR of both colonies developed normal febrile and hypothermic responses, thus suggesting that transport of amphipathic mediators by albumin is not indispensable for LPS signaling. Although alternative carrier proteins [such as alpha(1)-acid glycoprotein (AGP)] are known to assume transport functions of albumin in NAR, it is unknown whether inflammatory mediators are capable of inducing their actions when bound to alternative carriers. To test whether PAF, the most potent amphipathic pyrogen, causes fever when administered in an AGP-bound form was our second aim. Sprague-Dawley rats were preimplanted with jugular catheters, and their thermal responses to infusion of a 1:1 [PAF-AGP] complex (40 nmol/kg i.v.), AGP (40 nmol/kg i.v.), or various doses of free (aggregated) PAF were studied. The complex, but neither free PAF nor AGP, caused a high ( approximately 1.5 degrees C) fever with a short (< 10 min) latency. This is the first demonstration of a pyrogenic activity of AGP-bound PAF. We conclude that, in the absence of albumin, AGP and possibly other carriers participate in immune-to-brain signaling by binding and transporting amphipathic inflammatory mediators.
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PMID:Albumin is not an irreplaceable carrier for amphipathic mediators of thermoregulatory responses to LPS: compensatory role of alpha1-acid glycoprotein. 1557 66

Infectious challenge triggers a broad array of coordinated changes within the host organism, including alterations in sleep-wake behavior and body temperature. Pro-inflammatory cytokines orchestrate many of the behavioral, metabolic, and endocrine responses to immune challenge. Although interleukin (IL)-6 mediates several aspects of sickness behavior, a role for this cytokine as a mediator of alterations in sleep in response to immune challenge has not been established. We evaluated sleep-wake behavior and core body temperature of IL-6-deficient (IL-6 KO; B6.129S6-Il6tm1Kopf) mice and C57BL/6J control mice after intraperitoneal (IP) administration of 10 microg lipopolysaccharide (LPS). Because feedback mechanisms that regulate responses to immune challenge exhibit circadian rhythms, we evaluated responses to LPS administered at the beginning of both the light and dark portions of the light:dark cycle. LPS-induced increases in non-rapid eye movements sleep (NREMS) of both mouse strains, but this increase was less pronounced in IL-6 KO mice than in C57BL/6J mice. Strain differences in LPS-induced increases in NREMS were greatest after light-onset administration. During the 12 h light period, NREMS of C57BL/6J mice increased from 53.0+/-1.7% of recording time after vehicle to 65.4+/-1.4% of recording time after LPS. During this same time period, NREMS of IL-6 KO mice increased from 50.5+/-1.8% after vehicle to only 52.4+/-1.8% of recording time after LPS. REMS of both mouse strains was suppressed to the same extent after LPS, irrespective of timing of administration. LPS-induced fever in C57BL/6J mice, with peak magnitude of 1.4+/-0.3 degrees C and 1.8+/-0.2 degrees C after dark onset and light onset administration, respectively. In contrast, this dose of LPS-induced profound hypothermia in IL-6 KO mice, with nadirs of hypothermia reaching 4.9+/-1.0 degrees C after injection at dark onset and 2.2+/-0.5 degrees C after administration at light onset. These results indicate that IL-6 mediates some of the effects of LPS on NREMS and body temperature of mice, and that the magnitude and duration of these effects differ as a function of the time at which the challenge is given.
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PMID:Diurnal variation of lipopolysaccharide-induced alterations in sleep and body temperature of interleukin-6-deficient mice. 1558 37

TRPV1, the capsaicin receptor, is expressed not only in nociceptive neurons, but also in other locations, including the hypothalamus. Studies involving systemic or intrahypothalamic capsaicin administration have suggested a role for TRPV1 in body temperature control. To explore this possibility, we examined thermoregulatory responses in TRPV1-/- mice. These mutant animals exhibited no obvious changes in circadian body temperature fluctuation, tolerance to increased (35 degrees C) or decreased (4 degrees C) ambient temperature or ethanol-induced hypothermia. In contrast, fever production in response to the bacterial pyrogen, lipopolysaccharide (LPS) was significantly attenuated in TRPV1-/- mice. Despite this finding, we detected no significant differences between TRPV1-/- and control mice in the extent of LPS-induced c-Fos expression in numerous fever-related brain subregions. These results suggest that TRPV1 participates in the generation of polyphasic fever, perhaps at sites outside the brain.
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PMID:Attenuated fever response in mice lacking TRPV1. 1576 67

The urocortin1 (Ucn1) neurons of the mid-brain-localized Edinger-Westphal nucleus (EW) are robustly responsive to ethanol (EtOH) administration, and send projections to the dorsal raphe nucleus (DRN), which contains corticotropin-releasing factor type 2 receptors (CRF2) that are responsive to Ucn1. In addition, the DRN has been shown to be involved in regulation of body temperature, a function greatly affected by EtOH administration. The goal of the present study was to identify the role that the urocortinergic projections from the EW to the DRN have in mediating EtOH-induced and lipopolysaccharide (LPS)-induced hypothermia. Male C57BL6/J mice were used. Groups of mice underwent cannulation of the DRN, and then received i.p. injections of EtOH (2g/kg) or LPS (600 microg/kg or 400 microg/kg), followed by intra-DRN injections of artificial cerebrospinal fluid (aCSF) or anti-sauvagine (aSVG) (55 pmol), a CRF2 antagonist. Separate groups of mice received single intra-DRN injections of Ucn1 (20 pmol), CRF (20 pmol) or aCSF. For all experiments, core temperatures were monitored rectally every 30 min for several hours post-injection. Both EtOH and LPS induced hypothermia, and aSVG significantly attenuated this effect after EtOH; however, there was no significant attenuation of hypothermia after either dose of LPS. Ucn1 injection also caused hypothermia, while CRF injection did not. These data demonstrate that EtOH-induced hypothermia, but not LPS-induced hypothermia, may involve Ucn1 from EW acting at CRF2 receptors in the DRN.
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PMID:Ethanol versus lipopolysaccharide-induced hypothermia: involvement of urocortin. 1596 90

Exposing vertebrates to pathogenic organisms or inflammatory stimuli, such as bacterial lipopolysaccharide (LPS), activates the immune system and triggers the acute phase response. This response involves fever, alterations in neuroendocrine circuits, such as hypothalamo-pituitary-adrenal (HPA) and -gonadal (HPG) axes, and stereotypical sickness behaviors that include lethargy, anorexia, adipsia, and a disinterest in social activities. We investigated the hormonal, behavioral, and thermoregulatory effects of acute LPS treatment in a seasonally breeding songbird, the white-crowned sparrow (Zonotrichia leucophrys gambelii) using laboratory and field experiments. Captive male and female sparrows were housed on short (8L:16D) or long (20L:4D) day lengths and injected subcutaneously with LPS or saline (control). LPS treatment activated the HPA axis, causing a rapid increase in plasma corticosterone titers over 24 h compared to controls. Suppression of the HPG axis occurred in long-day LPS birds as measured by a decline in luteinizing hormone levels. Instead of a rise in body temperature, LPS-injected birds experienced short-term hypothermia compared to controls. Birds treated with LPS decreased activity and reduced food and water intake, resulting in weight loss. LPS males on long days experienced more weight loss than LPS males on short days, but this seasonal effect was not observed in females. These results paralleled seasonal differences in body condition, suggesting that modulation of the acute phase response is linked to energy reserves. In free-living males, LPS treatment decreased song and several measures of territorial aggression. These studies highlight immune-endocrine-behavior interrelationships that may proximately mediate life-history tradeoffs between reproduction and defense against pathogens.
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PMID:Hormonal, behavioral, and thermoregulatory responses to bacterial lipopolysaccharide in captive and free-living white-crowned sparrows (Zonotrichia leucophrys gambelii). 1596 47

Systemic inflammation is accompanied by changes in body temperature, either fever or hypothermia. Over the past decade, the rat and mouse have become the predominant animal models, and new species-specific tools (recombinant antibodies and other proteins) and genetic manipulations have been applied to study fever and hypothermia. Remarkable progress has been achieved. It has been established that the same inflammatory agent can induce either fever or hypothermia, depending on several factors. It has also been established that experimental fevers are generally polyphasic, and that different mechanisms underlie different febrile phases. Signaling mechanisms of the most common pyrogen used, bacterial lipopolysaccharide (LPS), have been found to involve the Toll-like receptor 4. The roles of cytokines (such as interleukins-1beta and 6 and tumor necrosis factor-alpha) have been further detailed, and new early mediators (e.g., complement factor 5a and platelet-activating factor) have been proposed. Our understanding of how peripheral inflammatory messengers cross the blood-brain barrier (BBB) has changed. The view that the organum vasculosum of the lamina terminalis is the major port of entry for pyrogenic cytokines has lost its dominant position. The vagal theory has emerged and then fallen. Consensus has been reached that the BBB is not a divider preventing signal transduction, but rather the transducer itself. In the endothelial and perivascular cells of the BBB, upstream signaling molecules (e.g., pro-inflammatory cytokines) are switched to a downstream mediator, prostaglandin (PG) E2. An indispensable role of PGE2 in the febrile response to LPS has been demonstrated in studies with targeted disruption of genes encoding either PGE2-synthesizing enzymes or PGE2 receptors. The PGE2-synthesizing enzymes include numerous phospholipases (PL) A2, cyclooxygenases (COX)-1 and 2, and several newly discovered terminal PGE synthases (PGES). It has been realized that the "physiological," low-scale production of PGE2 and the accelerated synthesis of PGE2 in inflammation are catalyzed by different sets of these enzymes. The "inflammatory" set includes several isoforms of PLA2 and inducible isoforms of COX (COX-2) and microsomal (m) PGES (mPGES-1). The PGE2 receptors are multiple; one of them, EP3 is likely to be a primary "fever receptor." The effector pathways of fever start from EP3-bearing preoptic neurons. These neurons have been found to project to the raphe pallidus, where premotor sympathetic neurons driving thermogenesis in the brown fat and skin vaso-constriction are located. The rapid progress in our understanding of how thermoeffectors are controlled has revealed the inadequacy of set point-based definitions of thermoregulatory responses. New definitions (offered in this review) are based on the idea of balance of active and passive processes and use the term balance point. Inflammatory signaling and thermoeffector pathways involved in fever and hypothermia are modulated by neuropeptides and peptide hormones. Roles for several "new" peptides (e.g., leptin and orexins) have been proposed. Roles for several "old" peptides (e.g., arginine vasopressin, angiotensin II, and cholecystokinin) have been detailed or revised. New pharmacological tools to treat fevers (i.e., selective inhibitors of COX-2) have been rapidly introduced into clinical practice, but have not become magic bullets and appeared to have severe side effects. Several new targets for antipyretic therapy, including mPGES-1, have been identified.
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PMID:Fever and hypothermia in systemic inflammation: recent discoveries and revisions. 1597 Apr 87

Transforming growth factor-beta (TGF-beta) is an important suppressor of inflammation. However, TGF-beta has also been found to promote secretion of inflammatory cytokines, and transgenic mice, which constitutively express TGF-beta in liver, have been found to be more susceptible to endotoxemia. To approach this apparent paradox, we investigated the role of hepatic TGF-beta1 in endotoxemia by utilising inducible TGF-beta1-transgenic mice that express TGF-beta1 under control of the C-reactive protein promoter. In contrast to non-transgenic littermates, administration of lipopolysaccharide (LPS) induced strongly increased expression of TGF-beta and acute phase proteins in the TGF-beta1-transgenic mice. Hepatic TGF-beta1-expression in the transgenic mice started an inflammatory cytokine cascade, marked by increased and prolonged secretion of TNF-alpha and IL-6 by hepatocytes. The inflammatory response of the TGF-beta1-transgenic mice to LPS was associated with high rates of mortality due to endotoxemic shock, marked by systemic hypotension and hypothermia. Endotoxemic shock was primarily mediated by TNF-alpha and IL-6, since inhibitory antibody to TNF-alpha or, more effectively, to IL-6 could reduce mortality in these mice. In conclusion, while TGF-beta-signalling to immune cells may suppress inflammatory effector function, TGF-beta-signalling to liver cells seems to promote LPS-stimulated secretion of inflammatory cytokines and to predispose for lethal endotoxemic shock.
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PMID:Hepatic over-expression of TGF-beta1 promotes LPS-induced inflammatory cytokine secretion by liver cells and endotoxemic shock. 1605 5

Restraint stress, lipopolysaccharide (LPS), and ethanol (EtOH) administration have all been found to induce c-Fos in the brain, and to cause hypothermia. The present study was designed to assess whether the c-Fos expression that occurs in the Edinger-Westphal nucleus (EW) after EtOH administration is independent of the hypothermia or any stress effects that occur. To test this, we used restraint stress and LPS in addition to EtOH, and also examined two control areas, the dorsal raphe nucleus (DRN) and the periaqueductal gray (PAG), in addition to EW. Male C57BL6/J mice were used. Groups of mice received intraperitoneal (IP) injections of EtOH (2 g/kg), LPS (600 microg/kg or 50 microg/kg), or saline. A separate group of mice received no injection, but were placed in plastic restrainers for the entirety of the experiment. For all groups, core temperatures were monitored rectally every 30 min for 3 h postinjection, after which, the animals were sacrificed. Then, the number of Fos-positive cells in the brain regions of the EW, DRN, and PAG was quantified. Both EtOH and restraint stress induced a transient hypothermia, where core temperature (Tc) declined immediately and then rose again. Both doses of LPS induced a slower developing, longer lasting hypothermia, while saline had no effect on Tc. Only EtOH induced a significant amount of c-Fos in EW, while both doses of LPS and restraint stress induced c-Fos in DRN, and only restraint stress caused induction in PAG. These data demonstrate that activation of EW after EtOH is unrelated to hypothermia or stress.
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PMID:Expression of c-Fos in the mouse Edinger-Westphal nucleus following ethanol administration is not secondary to hypothermia or stress. 1627 76

Vasodilatory prostanoids, such as prostacyclin and PGE2, and pro-inflammatory cytokines are known to play a central role in the pathogenesis of endotoxemia. This study was undertaken to elucidate whether indomethacin (INDO), a non-selective COX inhibitor, has protective effects against the cardiovascular alterations that occur during endotoxemia. Sprague-Dawley rats were injected intraperitoneally with 15 mg/kg lipopolysaccharide (LPS). LPS injection led to a prominent decrease in cardiac left ventricular end diastolic area (LVEDA) and increased LV fractional shortening (FS), as measured by echocardigraphy. LPS also led to a significant increase in plasma and myocardial TNF-alpha and IL-1beta levels, and elevated plasma and hypothalamic levels of PGE2. Neither the decrease in LVEDA and the increase in FS, nor the elevation in plasma and myocardial cytokine levels were altered by INDO (10 mg/kg). On the other hand, pretreatment with INDO significantly reduced the elevation in PGE2 and the hypothermia induced by LPS. Taken together, this study demonstrates that solely inhibiting the production of PGE2 is not sufficient to reduce the cardiovascular alteration seen in endotoxemia.
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PMID:Inhibition of prostaglandins does not reduce the cardiovascular changes during endotoxemia in rats. 1634 78

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