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)

Human recombinant IL-1 beta was able to kill C3H/HeJ mice only when inoculated intravenously at very high doses. IL-1 beta, inoculated at 100 mg/kg i.v. as a bolus, induced a shock-like state characterized by anorexia, severe hypothermia and hypoglycemia and persistent neutrophilia, leading to death in 55% of animals generally between 24 and 48 h. In contrast, the noninflammatory adjuvant IL-1 beta peptide VQGEESNDK (position 163-171) did not induce any toxic effect in vivo, when administered following the same schedule. At variance with what was previously observed in endotoxin induced shock, IL-1 beta induced death was not preceded by appearance of circulating TNF. On the other hand, very high and persistent levels of circulating IL-6 could be detected after lethal IL-1 beta administration. Treatment of mice with ibuprofen or with chlorpromazine, both known to counteract some of the toxic effects of IL-1 in vivo, could protect from IL-1 beta induced mortality. Both drugs, at doses protecting from IL-1 beta induced death, were able to abolish IL-1 beta-induced rise of circulating phospholipase A2 (PLA2) activity, and the subsequent generation of toxic PLA2-derived metabolites.
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PMID:Mechanism of acute toxicity of IL-1 beta in mice. 187 93

We examined the effects of intravenous (IV) or intracerebro-ventricular (ICV) injection of prostaglandin E2 (PGE2) on the rectal temperature of restrained rats. The IV injection of PGE2 (0.5 mg/kg) caused hypothermia in rats with high initial rectal temperatures, but caused an elevation in rectal temperature in those animals whose starting temperatures were low. In contrast, the ICV injection of PGE2 induced fever, regardless of the rectal temperature at the time of injection. We also examined whether temperature changes due to the IV injection of endotoxin (lipopolysaccharide, LPS, 10 micrograms/kg) or interleukin-1 beta(IL-1 beta, 0.2 micrograms/kg) were dependent upon the rats' initial rectal temperatures. Rats with low rectal temperatures developed fevers in response to LPS, while animals with high starting temperatures showed hypothermia. In contrast, the IV injection of IL-1 beta produced fever regardless of initial rectal temperature. These data suggest that PGE2 acts centrally to cause fever and peripherally to cause hypothermia, and that following the injection of LPS, these opposing actions of PGE2 may act together to determine the thermoregulatory response.
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PMID:The effect of prostaglandin E2 on the body temperature of restrained rats. 194 25

The ability of Escherichia coli-derived lipopolysaccharide (LPS), recombinant (r) interleukin 1-beta (rIL-1 beta), and r murine tumor necrosis factor-alpha (rMuTNF-alpha) to induce interleukin 6 (IL-6) production in vivo was investigated. Peak serum IL-6 concentration was attained after 2 hr of LPS injection into mice. The coinjection of antiserum against rMuTNF-alpha with LPS resulted in a reduction of the induced serum IL-6 level, indicating the involvement of endogenous TNF-alpha in LPS induction of IL-6. Recombinant IL-1 beta and rMuTNF-alpha injected directly caused the production of substantial amounts of IL-6 within 30 min. The injection of a combination of rIL-1 beta and rTNF-alpha induced a significantly greater level of IL-6 than either agent alone. The greater level of serum IL-6 was associated with hypothermia and an increased lethality among mice injected with both cytokines. These data demonstrate the abilities of IL-1 beta and TNF-alpha to induce IL-6 production in vivo and indicate that LPS induction of IL-6 may be mediated, at least partially, through TNF-alpha action. The data describe a new in vivo biologic activity shared between IL-1 beta and TNF-alpha and suggest that IL-6 may be an important effector in the manifestation of TNF-alpha and IL-1 beta actions in vivo.
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PMID:Endotoxin, tumor necrosis factor-alpha and interleukin 1 induce interleukin 6 production in vivo. 280 53

Significant morbidity and mortality associated with traumatic brain injury (TBI) are allied with secondary posttrauma inflammatory complications. Hypothermia has been suggested as a possible treatment to lessen or suppress these inflammatory reactions. We report here that interleukin 1 beta, a cytokine responsible for initiating inflammatory cascades, is elevated in rat cortex within 6 h of TBI in the rat. Nerve growth factor (NGF) RNA and protein also increased subsequently, and NGF protein remained elevated for up to 7 days. Four hours of whole body hypothermia (32 degrees C), applied immediately after the TBI, attenuated the posttrauma increase in IL-1 beta RNA and eliminated the increase in NGF RNA and protein observed in cerebral cortex following TBI. Thus, hypothermia may be an effective therapy to diminish the posttrauma inflammatory cascade in the brain (as suggested by the decrease in IL-1 beta). However, the same treatment may hinder the brain's intrinsic repair mechanisms. Optimal treatment may, therefore, require supplemental administration of neurotrophic factors or other agents along with hypothermia.
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PMID:Hypothermia attenuates the normal increase in interleukin 1 beta RNA and nerve growth factor following traumatic brain injury in the rat. 762 62

The role of endogenous corticoids in fever responses caused by recombinant murine interleukin (IL)-1 beta and IL-6 was studied in adult male Wistar rats. Adrenalectomy diminished the development of fever after intracerebroventricular (icv) injection of these ILs and lowered body temperature. Intraperitoneal administration of the same doses of ILs did not produce fever in intact animals or hypothermia in adrenalectomized rats, thus suggesting a central site of action of IL-1 beta and IL-6 in these experiments. Chronic replacement with moderate doses of corticosterone restored the fever response in adrenalectomized animals in response to icv administration of IL-1 beta but only partially reversed the fever caused by IL-6. Adrenalectomized animals acutely treated with corticosterone and thereafter with either IL-1 beta or IL-6 developed fever more rapidly than did chronically corticosterone-treated animals. In intact animals corticosterone blocked the fever response to icv injected IL-1 beta. We propose that in the rat corticosterone acts in a bimodal manner on body temperature; it exerts a permissive central effect on the fever response and limits the production of inflammatory mediators in the brain. Conversely, higher corticosterone doses probably reduce the magnitude of the fever response.
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PMID:Corticosterone modulates interleukin-evoked fever in the rat. 820 20

The neuropathological outcome of metabolic, vascular or mechanical insults to the CNS depends on brain temperature; mild hypothermia is neuroprotective, whereas elevated brain temperature can cause additional neural damage. Studies in both animals and humans have shown that the core and the brain temperature do not always concur with one another. It is therefore important to develop methods for monitoring brain temperature. This paper describes an animal model (the rat) in which we have developed a method to measure, at thermoneutral ambient temperature, the brain and core temperature concomitantly, during different drug treatments. We have used this animal model to study body temperature during fever (induced by human recombinant IL-1 beta, 5 microgram/kg, i.p.), stress-induced hyperthermia (handling of the animal), hypothermia (induced by (+/-)-8-hydroxy-2-dipropylaminotetralin hydrobromide, 0.5 mg/kg, i.p. ) and sleep (non-induced, other than by light and diurnal variation). We show that the thermal curves are similar in the brain and the peritoneum, independent of the thermal state.
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PMID:Simultaneous measurement of brain and core temperature in the rat during fever, hyperthermia, hypothermia and sleep. 973 Jun 92

We have shown previously that febrile range temperatures modify cytokine production by adult macrophages. In this study, we compared the effects of moderate hyperthermia and hypothermia on the kinetics of lipopolysaccharide (LPS)-induced cytokine expression in monocytes and macrophages of newborns and adults. During culture at 40 degrees C, the initial rates of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion were preserved, but the duration of secretion was shorter than the duration at 37 degrees C. TNF-alpha and IL1-beta concentrations in 24-h 40 degrees C culture supernatants were reduced 18%-50%. IL-6 concentration in 24-h 40 degrees C cultures was reduced 26%-29% in all cells except adult macrophages. At 32 degrees C, changes in early (2 h) and sustained (24 h) cytokine expression were reversed compared with those caused by hyperthermia. Culturing adult macrophages at 32 degrees C blunted early secretion of TNF-alpha and IL-6 by 69% and 65%, respectively, and increased TNF-alpha concentration at 24 h by 48% compared with levels at 37 degrees C. In adult monocytes cultured at 32 degrees C, early IL-6 and IL-1 beta secretion was decreased 64% and 51%, respectively. We speculate that the burst/suppression cytokine profile at febrile temperatures might enhance early activation of host defenses and prevent prolonged exposure to potentially cytotoxic cytokines. Hypothermia, on the other hand, may worsen outcome in infections by delaying and prolonging cytokine production.
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PMID:Effects of hypothermia and hyperthermia on cytokine production by cultured human mononuclear phagocytes from adults and newborns. 1115 70

Proinflammatory cytokines and acute physical stress influence sympathetic nerve discharge (SND). Because interleukin-1 beta (IL-1 beta) produces physiological responses that require central neural integration and because the sympathetic nervous system mediates physiological responses to environmental stress, we hypothesized that IL-1 beta modulates SND responses to acute physical stress. Therefore, this study examined the effects of IL-1 beta (290 ng/kg iv) and mild hypothermia on renal and interscapular brown adipose tissue (IBAT) SND regulation in chloralose-anesthetized rats. IBAT SND did not change after IL-1 beta administration but was significantly increased during acute mild hypothermia, which was induced 60 min after IL-1 beta treatment. Renal SND was unchanged after IL-1 beta administration and during hypothermia. Acute hypothermia, without prior IL-1 beta administration, did not alter IBAT and renal SND. Increases in IBAT SND during sustained (120 min) hypothermia were significantly higher in IL-1 beta-treated rats compared with saline-treated rats, whereas renal SND responses to sustained hypothermia did not differ among groups. Exposure to acute cold stress after sustained hypothermia produced greater increases in IBAT SND in IL-1 beta-treated rats compared with saline-treated controls. These data suggest that IL-1 beta alters IBAT SND responses to acute and sustained hypothermia.
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PMID:Interleukin-1 beta alters brown adipose tissue but not renal sympathetic nerve responses to hypothermia. 1170 10

Poly inosinic:poly cytidylic acid (poly I:C) is a synthetic double-stranded RNA and is a ligand for the Toll like receptor-3. This receptor is involved in the innate immune response to viral infection and poly I:C has been used to mimic the acute phase of a viral infection. The effects of TLR3 activation on brain function have not been widely studied. In the current study we investigate the spectrum of sickness behavioural changes induced by poly I:C in C57BL/6 mice and the CNS expression of inflammatory mediators that may underlie this. Poly I:C, at doses of 2, 6 and 12 mg/kg, induced a dose-responsive sickness behaviour, decreasing locomotor activity, burrowing and body weight, and caused a mild hyperthermia at 6h. The 12 mg/kg dose caused significant hypothermia at later times. The Remo400 remote Telemetry system proved a sensitive measure of this biphasic temperature response. The behavioural responses to poly I:C were not significantly blunted upon a second poly I:C challenge either 1 or 3 weeks later. Plasma concentrations of IL-6, TNF-alpha and IFN-beta were markedly elevated and IL-1 beta was also detectable. Cytokine synthesis within the CNS, as determined by quantitative PCR, was dominated by IL-6, with lesser inductions of IL-1 beta, TNF-alpha and IFN-beta and there was a clear activation of cyclooxygenase-2 at the brain endothelium. These findings demonstrate clear CNS effects of peripheral TLR3 stimulation and will be useful in studying aspects of the effects of systemic viral infection on brain function in both normal and pathological situations.
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PMID:The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic double-stranded RNA (poly I:C). 1732 19

Ischemic-reperfusion injury (IRI) can affect many organ systems. Examples include strokes, coronary occlusion, accidental hypothermia, compartment syndrome and neonatal hypoxia. To date no mechanism has been fully accepted to explain acute inflammation associated with IRI. There is circumstantial evidence from animal and human ex-vivo cardiac experiments to support the hypothesis that acute inflammation associated with IRI is in part caused by IL-1 beta and/or IL-1 alpha secretion. Danger signal formation, such as uric acid/calcium pyrophosphate crystallization and other cellular stresses, may occur in IRI. These in turn may stimulate innate immune pathways (i.e. cryopyrin-inflammasome; and/ or toll-like receptors 2 and 4) to secrete IL-1 beta. Most IL-1 targeted therapy studies have focused on chronic human diseases and hopefully this discussion will create a framework to encourage use of this therapy in acute inflammation associated with IRI.
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PMID:Ischemic-reperfusion syndromes: biochemical and immunologic rationale for IL-1 targeted therapy. 1847 71


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