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

Rats have an attenuated febrile response to exogenous (e.g. bacterial endotoxin) and endogenous pyrogen (e.g. interleukin-1beta) near the term of pregnancy, the mechanism of which is unknown. The present experiments were carried out on 71 non-pregnant and 181 pregnant Sprague-Dawley rats to determine if basal levels of the endogenous antipyretic substance, interleukin-1 receptor antagonist (IL-1ra), change relative to interleukin-1beta (IL-1beta) throughout gestation. Furthermore, we have constructed complete Escherichia coli lipopolysaccharide (LPS) dose-core temperature response curves in non-pregnant and pregnant rats on days 10, 15 and 20 of gestation (term of gestation approximately 21 days) to determine if the attenuated febrile response near the term of pregnancy results from a simple shift of the dose-response relationship or results from a dampening of the overall dose-response relationship. Basal IL-1beta, as determined by ELISA on trunk blood from non-pregnant and pregnant rats on days 10, 15 and 20 of gestation (d10, d15, d20), did not change significantly during pregnancy. Basal IL-1ra, however, was increased significantly in d15 rats as compared to non-pregnant, and d10 and d20 rats. The attenuated febrile response near the term of pregnancy, as determined by biotelemetry, did not result from a simple shift of the E. coli LPS dose-core temperature response curve but rather a dampening of the overall dose-response relationship. The febrile responses to EC(50) and EC(100) doses of E. coli LPS were preceded by a period of hypothermia, and were delayed and attenuated near the term of pregnancy as compared to that observed early in pregnancy and in non-pregnant rats. Our data provide evidence that pregnant rats are more sensitive to the hypothermia-producing effects of E. coli LPS than are non-pregnant rats and allow us to speculate that elevated basal IL-1ra may play a role in mediating the attenuated febrile response to pyrogen on day 15 but not on day 20 of gestation in rats.
 ...
PMID:Influence of pregnancy on plasma cytokines and the febrile response to intraperitoneal administration of bacterial endotoxin in rats. 1460 73

Excitotoxic brain injury is associated with hyperthermia, and there are data showing beneficial effects of hypothermia on neurodegeneration and that hyperthermia facilitates the neurodegeneration. Cytokines are inflammatory proteins that seem to be involved in the neuroinflammation associated with epilepsy. Core temperature changes caused by the epileptogenic glutamate analogue kainic acid (KA) were investigated in relation to changes in levels of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), and the endogenous interleukin-1 receptor antagonist (IL-1ra). The temperature was measured every 10 min during the first hour, and at 90 and 120 min, and hourly until 8 h after KA-injection (10 mg/kg). The cytokines were measured in the hypothalamus, a site of temperature regulation, and in hippocampus, cerebellum, and frontal cortex. KA induced a brief hypothermia followed by hyperthermia. IL-1beta levels were increased after KA-administration in all brain regions examined and, excepting hippocampus, returned to baseline levels at 24 h. The hippocampal IL-1ra levels were significantly increased at 24 h, whereas no changes in IL-6 levels were observed. The changes in IL-1beta levels and in ratios between the levels of the three cytokines, may account for some of the temperature changes and the behavioural manifestations induced by KA.
 ...
PMID:The influence of kainic acid on core temperature and cytokine levels in the brain. 1695 Jun 33

Despite the widespread interest in the clinical applications of hypothermia, the cellular mechanisms of hypothermia-induced neuroprotection have not yet been clearly understood. Therefore, the aim of this study was to elucidate the cellular effects of clinically relevant hypothermia and rewarming on the morphological and functional characteristics of microglia. Microglial cells were exposed to a dynamic cooling and rewarming protocol. For stimulation, microglial cells were treated with 1 microg/mL lipopolysaccharide (LPS). We found that hypothermia led to morphological changes from ramified to ameboid cell shapes. At 2 h after hypothermia and rewarming, microglial cells were again ramified with extended branches. Moreover, we found enhanced cell activation after rewarming, accompanied by increased phagocytosis and adenosine triphosphate consumption. Interestingly, hypothermia and rewarming led to a time-dependent significant up-regulation of the anti-inflammatory cytokines interleukin-10 and interleukin-1 receptor antagonist in stimulated microglial cells. This is in line with the reduced proliferation and time-dependent down-regulation of the pro-inflammatory cytokines tumor necrosis factor-alpha and monocyte chemotactic protein-1 in comparison to normothermic control cells after LPS stimulation. Furthermore, degradation of the inhibitor of the nuclear transcription factor-kappaB (IkappaB-alpha) was diminished and delayed under conditions of cooling and rewarming in LPS-stimulated microglial cells. Thus, our results show that hypothermia and rewarming activate microglial cells, increase phagocytosis and shift the balance of cytokine release in stimulated microglial cells towards the anti-inflammatory cytokines. This could be a new cellular mechanism of hypothermia-induced neuroprotection mediated by activated microglial cells.
 ...
PMID:Mechanisms of hypothermia-induced cell protection mediated by microglial cells in vitro. 2037 79