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)

The present study was undertaken to evaluate: (1) whether lipopolysaccharide LPS-induced hypothermic responses may be altered during two estrous cycle phases, proestrus and diestrus, and after ovariectomy, followed by hormonal supplementation and (2) whether nitric oxide (NO) plays a role on LPS-induced hypothermia responses in female mice. Experiments were performed on adult female wild-type (WT) C57BL and inducible NO synthase knockout (KO) mice weighing 18 to 30 g. Endotoxemia was induced by intraperitoneal LPS administration from Escherichia coli at a nonlethal dose of 10 mg/kg, and body temperature was measured by biotelemetry. Hormonal replacement was performed in ovariectomized mice through 17beta-estradiol Silastic capsules (100 mug) and s.c. injection of progesterone (0.5 mg per animal). We observed that during the diestrus phase, mice presented more intensive hypothermia than during proestrus phase, and hormonal supplementation with 17beta-estradiol and progesterone attenuated hypothermia in ovariectomized mice. During diestrus and ovariectomy, KO mice had higher hypothermic response when compared with the WT group. During proestrus, the lack of statistical difference between KO and WT mice could be consequent of lower ovarian hormones plasma levels. After hormonal replacement, hypothermia was reverted in KO groups probably because of higher ovarian hormonal levels. In summary, the results demonstrated that NO release by inducible NO synthase has an important thermoregulatory role in LPS-induced hypothermia in female mice. Besides, this involvement is directly dependent on the presence of ovarian hormones and their respective levels.
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PMID:Hypothermia during endotoxemic shock in female mice lacking inducible nitric oxide synthase. 1762 Dec 53

We tested the hypothesis that laminarin (LAM), a beta (1-3) polysaccharide extracted from brown algae, can modulate the response to a systemic inflammation. Male Wistar rats (n=7 per group) were fed a standard diet (control) or a diet supplemented with LAM for 25 days (5% during 4 days followed by 10% during 21 days). Thereafter, Escherichia coli lipopolysaccharides (LPS; 10 mg/kg i.p.) were injected and the animals were sacrificed 24 h after LPS challenge. The hypothermia, hyperglycemia and hypertriglyceridemia occurring early after LPS administration were less pronounced in LAM-treated rats than in controls. The increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities - reflecting hepatic alterations - was lessened after LPS injection in LAM-treated rats compared to control rats. LAM treatment decreased serum monocytes number, nitrite (NO2) and tumor necrosis factor-alpha (TNF-alpha). LAM also modulated intra-hepatic immune cells: it lowered the occurrence of peroxidase-positive cells (corresponding to monocytes/neutrophils) and, in contrast, it increased the number of ED2-positive cells, corresponding to resident hepatic macrophages, i.e. Kupffer cells. In conclusion, the hepatoprotective effect of marine beta (1-3) glucan during endotoxic shock may be linked to its immunomodulatory properties. We propose that both lower recruitment of inflammatory cells inside the liver tissue and lower secretion of inflammatory mediators play a role in the tissue protective effect of LAM. These effects could be due to a direct effect of beta-glucan on immune cells, or to an indirect effect through their dietary fibre properties (fermentation in the gut).
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PMID:Dietary supplementation with laminarin, a fermentable marine beta (1-3) glucan, protects against hepatotoxicity induced by LPS in rat by modulating immune response in the hepatic tissue. 1827 7

Acetaminophen (AC) reduces the core temperatures (T(c)) of febrile and non-febrile mice alike. Evidence has been adduced that the selectively AC-sensitive PGHS isoform, PGHS-1b (COX-3), mediates these effects. PGHS-1b, however, has no catalytic potency in mice. To resolve this contradiction, AC was injected intravenously (i.v.) into conscious PGHS-1 gene-sufficient (wild-type (WT)) and -deficient (PGHS-1(-/-)) mice 60 min before or after pyrogen-free saline (PFS) or E. coli LPS (10 microg/kg) i.v. T(c) was monitored continuously; brain and plasma PGE(2) levels were determined hourly. AC at <160 mg/kg did not affect T(c) when given before PFS or LPS; at 160 mg/kg, it caused a approximately 2.5 degrees C T(c) fall in 60 min. LPS given after AC (all doses) induced a approximately 1 degrees C fever, not different from that in AC-untreated mice. But this rise was insufficient to overcome the hypothermia of the 160 mg/kg-treated mice; their T(c) culminated 1 degrees C below baseline. LPS given before AC similarly elevated T(c) approximately 1 degrees C. This rise was reduced to baseline in 30 min by 80 mg AC/kg; T(c) rebounded to its febrile level over the next 30 min. At 160 mg/kg, AC reduced T(c) to 4 degrees C below baseline in 60 min, where it remained until the end of the experiment. WT and PGHS-1(-/-) mice responded similarly to all the treatments. The basal brain and plasma PGE(2) levels of PFS mice and the elevated plasma levels of LPS mice were unchanged by AC at 160 mg/kg; but the latter's brain levels were reduced at 1h, then recovered. Thus, AC could exert an anti-PGHS-2 effect when this enzyme is upregulated in the brain of febrile mice. The hypothermia it induces in non-febrile mice, therefore, is due to another mechanism. PGHS-1b is not involved in either case.
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PMID:Acetaminophen: antipyretic or hypothermic in mice? In either case, PGHS-1b (COX-3) is irrelevant. 1808 54

It has been demonstrated that chicken TRPV1 (transient receptor potential vanilloid of subtype-1) is insensitive to capsaicin (CAP), and therefore, a chicken model is suitable to analyze the CAP-sensitive TRPV1-independent pathway. We elucidated here the possible involvement of the pathway in hypothermia induced by bacterial endotoxin (lipopolysaccharide, LPS) in chickens. Chicks were pretreated with CAP (10 mg/kg, iv) at 1, 2 and 3 days of age to desensitize them towards the CAP-sensitive pathway. An intravenous injection of LPS in 4-day-old chicks caused progressive hypothermia, ending with collapse and 78% mortality within 12 h after injection. The CAP pretreatment rescued the LPS-induced endotoxin shock and hypothermia in chicks. LPS-induced iNOS expression as well as NO production in liver and lung was suppressed by CAP pretreatment. CAP pretreatment also attenuated hypothermia due to exposure of chicks to cold ambient temperature. These findings suggest that a CAP-sensitive TRPV1-independent pathway may be involved in pathophysiological hypothermic reactions through the mediation of NO in chickens.
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PMID:Capsaicin pretreatment attenuates LPS-induced hypothermia through TRPV1-independent mechanisms in chicken. 1847 76

Acute starvation attenuates the fever response to pathogens in several mammalian species. The underlying mechanisms responsible for this effect are not fully understood but may involve a compromised immune and/or thermoregulatory function, both of which are prerequisites for fever generation. In the present study, we addressed whether the impaired innate immune response contributes to the reported attenuation of the fever response in fasted rats during LPS-induced inflammation. Animals fasted for 48 h exhibited a significant and progressive hypothermia prior to drug treatment. An intraperitoneal injection of LPS (100 microg/kg) resulted in a significantly attenuated fever in the fasted animals compared with the fed counterparts. This attenuation was accompanied by the diminution in the concentration of some [TNF and IL-1 receptor antagonist (RA)] but not all (IL-1beta and IL-6) of the plasma cytokines normally elevated in association with the fever response. Nevertheless, fasting had no effect on the LPS-induced inflammatory responses at the level of the brain, as assessed by mRNA expressions of inhibitory factor(I)-kappaB, suppressor of cytokine signaling (SOCS3), IL-1beta, cyclooxygenase (COX)-2, and microsomal PGE synthase (mPGES)-1 in the hypothalamus, as well as by PGE2 elevations in the cerebrospinal fluid. In contrast, fasting significantly attenuated the fever response to central PGE2 injection. These results show that fasting does not alter the febrigenic signaling from the periphery to the brain important for central PGE2 synthesis but does affect thermoregulatory mechanisms downstream of and/or independent of central PGE2 action.
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PMID:Immune-to-brain signaling and central prostaglandin E2 synthesis in fasted rats with altered lipopolysaccharide-induced fever. 1848 Feb 40

Fever is a non-specific host defense mechanism that comprises part of the innate immune response. Innate immune function is thought to be an important adaptive immunological response to infection because it occurs across a broad diversity of phyla. Some reptiles can mount a febrile response, despite the fact that their internal body temperatures (T(b)s) are, to some extent, controlled by the environmental temperatures in which they live. This study was undertaken to determine if LPS would induce fever in green anole lizards (Anolis carolinensis). Lizards were maintained in thermal gradients (22-45 degrees C) with a 12-h diurnal cycle. anoles were injected with LPS, pyrogen-free saline, or left untreated, and their T(b)s were recorded every 15min using internal cloacal probes. All lizards showed a diurnal periodicity in T(b) characterized by decreased temperatures during the scotophase (dark hours) and higher temperatures during the photophase (light phase). Anoles injected with LPS exhibited a hypothermic response, relative to untreated and saline-injected animals. The response varied from 2.1 to 4.6 degrees C lower than control lizards. The hypothermic response was initiated within 12-24h of LPS injection, and continued for 3 days after treatment. However, the anapyrexic response was observed primarily during scotophases, with photophase hypothermia observed only on the first day after LPS injection.
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PMID:Effects of bacterial lipopolysaccharide on thermoregulation in green anole lizards (Anolis carolinensis). 1851 28

We previously showed that hypothermia attenuates inflammation in focal cerebral ischemia (FCI) by suppressing activating kinases of nuclear factor-kappa B (NFkappaB). Here we characterize the inflammatory response in global cerebral ischemia (GCI), and the influence of mild hypothermia. Rodents were subjected to GCI by bilateral carotid artery occlusion. The inflammatory response was accompanied by microglial activation, but not neutrophil infiltration, or blood brain barrier disruption. Mild hypothermia reduced CA1 damage, decreased microglial activation and decreased nuclear NFkappaB translocation and activation. Similar anti-inflammatory effects of hypothermia were observed in a model of pure brain inflammation that does not cause brain cell death. Primary microglial cultures subjected to oxygen glucose deprivation (OGD) or stimulated with LPS under hypothermic conditions also experienced less activation and less NFkappaB translocation. However, NFkappaB regulatory proteins were not affected by hypothermia. The inflammatory response following GCI and hypothermia's anti-inflammatory mechanism is different from that observed in FCI.
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PMID:Inflammation and NFkappaB activation is decreased by hypothermia following global cerebral ischemia. 1906 68

Systemic inflammation is associated with either fever or hypothermia. Fever, a response to mild systemic inflammation, is mediated by cyclooxygenase (COX)-2 and not by COX-1. However, it is still disputed whether COX-2, COX-1, neither, or both mediate(s) responses to severe systemic inflammation, and, in particular, the hypothermic response. We compared the effects of SC-236 (COX-2 inhibitor) and SC-560 (COX-1 inhibitor) on the deep body temperature (T(b)) of rats injected with a lower (10 microg/kg i.v.) or higher (1,000 microg/kg i.v.) dose of LPS at different ambient temperatures (T(a)s). At a neutral T(a) (30 degrees C), the rats responded to LPS with a polyphasic fever (lower dose) or a brief hypothermia followed by fever (higher dose). SC-236 (2.5 mg/kg i.v.) blocked the fever induced by either LPS dose, whereas SC-560 (5 mg/kg i.v.) altered neither the febrile response to the lower LPS dose nor the fever component of the response to the higher dose. However, SC-560 blocked the initial hypothermia caused by the higher LPS dose. At a subneutral T(a) (22 degrees C), the rats responded to LPS with early (70-90 min, nadir) dose-dependent hypothermia. The hypothermic response to either dose was enhanced by SC-236 but blocked by SC-560. The hypothermic response to the higher LPS dose was associated with a fall in arterial blood pressure. This hypotensive response was attenuated by either SC-236 or SC-560. At the onset of LPS-induced hypothermia and hypotension, the functional activity of the COX-1 pathway (COX-1-mediated PGE(2) synthesis ex vivo) increased in the spleen but not liver, lung, kidney, or brain. The expression of splenic COX-1 was unaffected by LPS. We conclude that COX-1, but not COX-2, mediates LPS hypothermia, and that both COX isoforms are required for LPS hypotension.
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PMID:Cyclooxygenase-1 or -2--which one mediates lipopolysaccharide-induced hypothermia? 1951 80

Heart rate variability (HRV) falls in humans with sepsis, but the mechanism is not well understood. We utilized a mouse model of endotoxemia to test the hypothesis that cytokines play a role in abnormal HRV during sepsis. Adult male C57BL/6 mice underwent surgical implantation of probes to continuously monitor electrocardiogram and temperature or blood pressure via radiotelemetry. Administration of high-dose LPS (Escherichia coli LPS, 10 mg/kg, n = 10) caused a biphasic response characterized by an early decrease in temperature and heart rate at 1 h in some mice, followed by a prolonged period of depressed HRV in all mice. Further studies showed that LPS doses as low as 0.01 mg/kg evoked a significant decrease in HRV. With high-dose LPS, the initial drops in temperature and HR were temporally correlated with peak expression of TNFalpha 1 h post-LPS, whereas maximal depression in HRV coincided with peak levels of multiple other cytokines 3-9 h post-LPS. Neither hypotension nor hypothermia explained the HRV response. Pretreatment with dexamethasone prior to LPS significantly blunted expression of 7 of the 10 cytokines studied and shortened the duration of depressed HRV by about half. Interestingly, dexamethasone treatment alone caused a dramatic increase in both low- and high-frequency HRV. Administration of recombinant TNFalpha caused a biphasic response in HR and HRV similar to that caused by LPS. Understanding the role of cytokines in abnormal HRV during sepsis could lead to improved strategies for detecting life-threatening nosocomial infections in intensive care unit patients.
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PMID:Endotoxin depresses heart rate variability in mice: cytokine and steroid effects. 1965 3

Hyper-coagulation, hypothermia, systemic inflammatory responses and shock are major clinical manifestations of endotoxin shock syndrome in human. As previously reported, mice primed with heat-killed Propionibacterium acnes are highly susceptible to the action of LPS to induce tumour necrosis factor (TNF)-alpha and to that of TNF-alpha to trigger lethal shock. Here we investigated the mechanisms underlying the P. acnes-induced sensitization to LPS and TNF-alpha and the development of individual symptoms after subsequent challenge with LPS or TNF-alpha. Propionibacterium acnes-primed wild-type (WT) mice, but not naive mice, exhibited hyper-coagulation with elevated levels of thrombin-antithrombin complexes and anti-fibrinolytic plasminogen activator inhibitor 1 in their plasma, hypothermia, systemic inflammatory responses and high mortality rate after LPS or TNF-alpha challenge. Propionibacterium acnes treatment reportedly induces both T(h)1 and T(h)17 cell development. Propionibacterium acnes-primed Il12p40(-/-) and Ifngamma(-/-) mice, while not Il17A(-/-) mice, evaded all these symptoms/signs upon LPS or TNF-alpha challenge, indicating essential requirement of IL-12-IFN-gamma axis for the sensitization to LPS and TNF-alpha. Furthermore, IFN-gamma blockade just before LPS challenge could prevent P. acnes-primed WT mice from endotoxin shock syndrome. These results demonstrated requirement of IFN-gamma to the development of endotoxin shock and suggested it as a potent therapeutic target for the treatment of septic shock.
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PMID:IFN-gamma is a master regulator of endotoxin shock syndrome in mice primed with heat-killed Propionibacterium acnes. 2013 Feb 31


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