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

The effects of selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors (valeryl salicylate and SC-58236, respectively) on Escherichia coli O111:B4 lipopolysaccharide (LPS)-induced dual thermoregulatory changes and serum tumor necrosis factor-alpha elevation were investigated in rats. LPS (50 microg/kg, intraperitoneal) produced an initial hypothermia that was then followed by fever. Serum tumor necrosis factor-alpha levels elevated at the initial phase of hypothermia. Valeryl salicylate injections (20, 40, and 80 mg/kg, subcutaneous [s.c.]) completely inhibited hypothermia without any effect on the elevated serum tumor necrosis factor-alpha levels and on the subsequent fever. On the other hand, SC-58236 injections (10, 20, and 40 mg/kg, s.c.) only partially abolished the hypothermia. SC-58236 had no effect on the initiation of fever, however completely inhibited the maintenance of fever. The serum tumor necrosis factor-alpha elevation was not reduced by SC-58236 treatment. The combination of valeryl salicylate and SC-58236 also failed to inhibit the initiation of fever. These findings suggest that cycloxygenase-1 may have a predominant role for the development of LPS-induced hypothermia, but cyclooxygenase-1 does not seem to be involved in the mediation of LPS-induced fever. Meanwhile, cyclooxgenase-2 may be critical for the late phase rather than the initiation of the fever response in rats.
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PMID:Effects of selective cyclooxygenase enzyme inhibitors on lipopolysaccharide-induced dual thermoregulatory changes in rats. 1184 24

We have previously shown that Escherichia coli O111:B4 serotype lipopolysaccharide (LPS) produced a dual change in rectal temperature (Tb), in which hypothermia preceded fever at subthermoneutral ambient temperature (Tamb; 24-26 degrees C) in rats. In this study, the characteristics of the initial hypothermic response were evaluated. Hypothermia was significant when LPS (50 microg/kg, i.p.) was injected at thermoneutral Tamb (30 degrees C). There was no heat loss through tail skin during hypothermia. The open field activity of the rats did not change during this period. However, serum levels of tumor necrosis factor-alpha (TNF-alpha) elevated at the beginning of the hypothermia, whereas serum levels of interleukin (IL)-1beta and interferon (IFN)-gamma remained unchanged. A nonselective cyclooxygenase inhibitor (indomethacin, 5 mg/kg, s.c.) inhibited hypothermia and serum TNF-alpha elevation, which resulted in an acceleration of the subsequent pyrogenic response. Moreover, a nonselective inhibitor of nitric oxide synthase (nitro L-arginine methyl ester (L-NAME), 10 mg/kg, s.c.) not only abolished fever but also prolonged the initial hypothermic response. These data suggest that the hypothermic component of low dose LPS-induced dual response is a regulated decrease in Tb. The data also suggest that hypothermia and fever may occur independently as two different thermoregulatory strategies against immune challenge in rats.
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PMID:Characterization of the hypothermic component of LPS-induced dual thermoregulatory response in rats. 1190 Jul 81

Hypothermia is associated with elevated frequency of infectious complications. Dysfunction of the immune response caused by hypothermia has been demonstrated in both clinical and animal studies, but it still remains unclear to what extent immunocompetent cells are directly influenced by hypothermia. To estimate the direct influence of mild hypothermia on cytokine expression and release by human peripheral blood mononuclear cells (PBMC), primary cultures of PBMC were incubated at 34 degrees C or 32 degrees C activated by lipopolysaccharide (LPS), phytohemagglutinin (PHA), or tumor necrosis factor-alpha (TNF-alpha). The cytokine gene expression was evaluated by RT-PCR. Release of interleukin-2 (IL-2), IL-6, IL-10, and TNF-alpha was measured by ELISA. Mild hyperthermia significantly impaired IL-2 gene expression in PHA-stimulated cultures of PBMC and decreased IL-2 release in all variants of cultures. Secretion of IL-6, IL-10, and TNF-alpha was decreased in hypothermic cultures of PBMC stimulated with the T lymphocyte activator PHA. Slight suppression of IL-10 secretion was observed also in TNF-alpha-stimulated hypothermic cultures of PBMC. TNF-alpha release increased slightly in mild hypothermia control cultures. Our data demonstrate that the direct influence of hypothermia on cytokine expression and release from PBMC is not uniform. Reduction of IL-2 production might play a crucial role in the impairment of immune response in hypothermia.
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PMID:Direct influence of mild hypothermia on cytokine expression and release in cultures of human peripheral blood mononuclear cells. 1191 4

Mild hypothermia is neuroprotective, but the reasons are not well known. Inflammation contributes to ischemic damage; therefore, we examined whether the protection by hypothermia may be attributable to alterations in the inflammation. We examined whether hypothermia might alter the inflammatory cell-associated inducible nitric oxide synthase (iNOS) and subsequent nitric oxide (NO) and peroxynitrite generation in experimental stroke and inflammation. Rats underwent 2 hr of middle cerebral artery occlusion (MCAO). Brain inflammation was modeled by intravenous lipopolysaccharide (LPS) (2 mg/kg) injection. Temperature was maintained at 33 degrees C for 2 hr immediately after MCAO and LPS injection, delayed 2 hr after MCAO or maintained at 38 degrees C. Cultured microglia were activated with LPS and then incubated at 33 or 37 degrees C. Both intraischemic and delayed mild hypothermia attenuated infarct size by 40% (p < 0.05). Immunohistochemistry was performed to identify cell type, iNOS, and peroxynitrite. The majority of iNOS- and peroxynitrite-positive cells were activated microglia-macrophages, and mild hypothermia significantly decreased the numbers of immunoreactive cells at 72 hr by >50% (p < 0.05). After ischemia, mild hypothermia decreased NO production by 40%. Similarly, hypothermia attenuated NO and iNOS in LPS-injected rats, as well as in cultured microglia. Aminoguanidine, an iNOS inhibitor, also attenuated infarct size and NO in ischemic and inflammation models. We conclude that mild hypothermia significantly inhibits the inflammatory response by affecting microglial iNOS-NO generation. Therapies directed against microglia or their activation may be useful in treating stroke.
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PMID:Influence of mild hypothermia on inducible nitric oxide synthase expression and reactive nitrogen production in experimental stroke and inflammation. 1201 11

Fever has had a long phylogenetic history: it occurs not only in infected birds and mammals, but also in infected reptiles, amphibians, fish and even insects. When these "cold-blooded" animals are prevented from adapting their body temperature to the risen thermoregulatory set-point by behavioral means, a more severe state of disease and a higher mortality are the consequences. It seems unlikely that an energy-dependent process, such as fever, would have been retained for hundreds of millions of years, in so many groups of organisms, if it provided no selective advantage. Fever may represent a leukocyte-based amplification mechanism to affect host challenge: enhanced motility of leukocytes, enhanced lymphocyte response to mitogens, increased production of interferon, enhanced immune response to viral antigens. Evidence for a beneficial effect of fever is also supported by the results of our animal experiments. Intraperitoneal injection of a high dose of bacterial lipopolysaccharide (LPS) in rats induces a septic shock like state which is accompanied by hypothermia on the day of LPS-administration and a robust fever on the following days. Co-injection of a neutralizing synthetic form of the soluble tumor necrosis factor (TNF) type 1 receptor completely neutralizes LPS-induced bioactive TNF in the lavage of the abdominal cavity and in blood plasma. Treatment with the TNF-antagonist results in much faster recovery from the hypothermic state. The rats develop pronounced fever already on the day of injection and there is significantly less reduction in body weight and food and water intake. Similar, but less pronounced effects can be induced by treatment with inhibitors of the inducible form of nitric oxide (NO)-synthase indicating that TNF-induced detrimental effects are, in part, mediated by excessive formation of NO. These results confirm that an accelerated onset of fever or a faster recovery from hypothermia in a septic state may have rather beneficial than maladaptive effects.
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PMID:[Fever in acute illness: beneficial or harmful?]. 1206 Sep 73

The effects of nimesulide and diclofenac on lipopolysaccharide (LPS)-induced rectal temperature changes and serum tumour necrosis factor (TNF)-alpha elevation were investigated in rats. LPS (Escherichia coli O111:B4; 50 microg/kg, intraperitoneally) produces a dual body temperature response, in which initial hypothermia precedes fever. Serum TNF-alpha levels rise during the initial phase of the induced hypothermia. Nimesulide, a preferential inhibitor of cyclooxygenase-2 (0.05, 0.5 or 1 mg/kg, subcutaneously) completely abolished the hypothermia, resulting in an acceleration of the fever phase. However, the peak and plateau phases of fever were not changed by nimesulide treatment. Nimesulide (0.5 mg/kg) partially prevented serum TNF-alpha elevation. The non-selective cyclooxygenase inhibitor diclofenac inhibited hypothermia at all doses tested (0.03, 0.3 or 3 mg/kg, subcutaneously) although fever was completely abolished at the 3 mg/kg dose only. Diclofenac also partially abolished the elevation in serum TNF-alpha levels, but at the highest dose only (3 mg/kg). These data suggest that nimesulide and diclofenac can preferentially inhibit LPS-induced hypothermia at doses that do not abolish fever in rats. Both these drugs also reduced elevated TNF-alpha levels, a fact which may, at least partly, explain the antihypothermic effect of nimesulide.
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PMID:Nimesulide and diclofenac inhibit lipopolysaccharide-induced hypothermia and tumour necrosis factor-alpha elevation in rats. 1257 19

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

Fever is a coordinated autonomic, endocrine, and behavioral response mediated by the brain in reaction to inflammatory stimuli. An essential step in transmitting the immune signal to the brain is the formation of prostaglandin E2. Cyclooxygenase (COX) is the critical enzyme in the synthesis of prostaglandins and COX-2, the inducible form of the enzyme, is markedly induced in cells associated with the cerebral blood vessels and the leptomeninges by immune stimuli such as intravenous administration of lipopolysaccharide (LPS). However, the specific roles of COX-1, the constitutive form of cyclooxygenase, and COX-2 in LPS-induced fever are not well understood. We injected LPS i.v. in combination with either a highly selective COX-1 (SC-560) or COX-2 (SC-236) inhibitor to determine the effects of each drug on the subsequent fever response and on the pattern of expression of Fos protein in the brain. The COX-2 inhibitor blocked LPS-induced fever and Fos expression in sites such as the ventromedial preoptic nucleus (VMPO) and the hypothalamic paraventricular nucleus (PVH), although Fos-immunoreactivity in the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM), and parabrachial nucleus (PB) remained. In contrast, the COX-1 inhibitor resulted in a profound hypothermic response to LPS and blocked LPS-induced Fos-immunoreactivity in the PVH, PB, NTS, and VLM, although it had no effect on the VMPO. Although COX-2 plays a dominant role in mediating fever responses to i.v. LPS, at least some components of the response, including avoiding hypothermia and the induction of Fos in the NTS, VLM, PB, and PVH, appear to depend on COX-1. J.
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PMID:Specific roles of cyclooxygenase-1 and cyclooxygenase-2 in lipopolysaccharide-induced fever and Fos expression in rat brain. 1281 98

We recently reported that hypothermia protects against intrapulmonary nitric oxide overproduction and nitric oxide-mediated lung injury in endotoxemic rats. Few studies have been performed to investigate whether hypothermia reduces inflammation by affecting favorable changes in chemokine and pro- and anti-inflammatory cytokine profiles. In this study, we tested the hypothesis that hypothermia decreases concentrations of growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1), interleukin (IL)-1beta, IL-6, and myeloperoxidase and increases concentration of IL-10 in the lungs endotoxemic rats. Twelve rats were anesthetized and randomized to treatment with either hypothermia (T = 18-24 degrees C; n = 6) or normothermia (T = 36-38 degrees C, n = 6). Endotoxin (15 mg/kg of Escherichia coli lipopolysaccharide) was administered intravascularly and lung tissue was harvested 150 min later. Three additional rats were sham instrumented and maintained as normothermic but not given endotoxin. Hematoxylin & eosin staining was performed for qualitative inspection of tissues. Quantitative analyses of lung homogenates were performed using enzyme-linked immunosorbent assays for IL-1beta, IL-6, IL-10, and GRO/CINC-1. Myeloperoxidase concentrations were determined using a colorimetric assay. Hypothermia attenuated the induction of intrapulmonary IL-1beta (P < 0.05), IL-6 (P < 0.05), GRO/CINC-1 (P < 0.05), and myeloperoxidase (P < 0.05) caused by endotoxin. Inspection of the lungs revealed that hypothermia similarly attenuated histological signs of injury, such as interstitial edema and neutrophil accumulation. Hypothermia increased the intrapulmonary concentration of IL-10 more than 3-fold over that measured in the normothermia (endotoxin-exposed) group (P < 0.05). Hypothermia inhibits neutrophil recruitment in the lungs of endotoxemic rats in part by decreasing proinflammatory cytokine expression. Additionally, hypothermia induces intrapulmonary IL-10 expression. Further studies are needed to investigate whether IL-10 mediates the anti-inflammatory effects of hypothermia.
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PMID:Hypothermia induces interleukin-10 and attenuates injury in the lungs of endotoxemic rats. 1281 67


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