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

A rough mutant of Escherichia coli (J5), which expresses a core lipopolysaccharide antigen common to gram-negative organisms on its cell surface, was used to immunize rabbits. Passively transferred anti-E. coli J5 rabbit antiserum (anti-J5 RS), normal rabbit serum (NRS), and saline were compared in a guinea pig model of intravenous gram-negative sepsis, with E. coli 0111:B4 and Pseudomonas aeruginosa as challenge organisms. Physiologic monitoring demonstrated a consistent pattern associated with gram-negative sepsis in this model: hypothermia, hypotension, bradycardia, a fall in white blood cell count and platelet count, and persistence of challenge organisms within the circulation. Pretreatment with anti-J5 RS prevented hypothermia and the fall in platelet count while augmenting bacterial clearance. Survival was markedly enhanced by anti-J5 RS, but not by NRS or saline. Concomitant heparin pretreatment was thought to be a significant factor in demonstrating the protective effect in this model. Parallel in vitro cross-reactivity measured by an enzyme-linked immunosorbent assay and an opsonization assay demonstrated that anti-J5 RS extensively cross-reacted with a variety of gram-negative bacilli. Demonstration of enhanced opsonization by anti-J5 RS of gram-negative organisms was thus well correlated with enhanced systemic clearance of bacteria and improved survival subsequent to intravenous bacterial challenge.
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PMID:Immunotherapy of gram-negative bacterial sepsis: enhanced survival in a guinea pig model by use of rabbit antiserum to Escherichia coli J5. 704 94

Activation of the immune system in response to either infection or lipopolysaccharide (LPS) produces neurophysiological, neuroendocrine and behavioral changes. Some of the physiological consequences of LPS are mediated by endogenous opioid peptides. The following studies were designed to characterize the effects of LPS in several behavioral paradigms, and to determine the role of opioids in mediating these effects. The effects of LPS on locomotor and self-care activity were assessed in the open field test. Rats were injected with either saline or a dose of LPS (25, 50, 100, or 1000 micrograms/kg). 4 h later, the animals were placed in an open field and the numbers of line crossings, rearings and grooming episodes were counted. LPS significantly suppressed the three open field behaviors in a dose-related manner. The effect of LPS on sensitivity to pain was determined using the hot-plate and tail-flick tests. Administration of LPS (200 micrograms/kg) increased pain sensitivity in the hot plate test 30 min after drug administration, but produced a significant analgesic response 4 h after drug administration in both tests. Further characterization of LPS-induced analgesia demonstrated that it began about 2 h after and disappeared 30 h after the administration of LPS. Administration of naltrexone completely blocked the analgesic effects of LPS 4 h after its administration, but had no effect on LPS-induced suppression of activity in the open field. The effect of LPS on body temperature was biphasic, producing hypothermia at 2 h and hyperthermia at 8-30 h after its administration. Naltrexone had no effect on the body temperature changes induced by LPS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavioral effects of lipopolysaccharide in rats: involvement of endogenous opioids. 792 30

Intraperitoneal injection of lipopolysaccharide (LPS) was used to elicit a sublethal, shock-like condition in mice. LPS, 2.5 mg/kg i.p., induced hypothermia, elevated serum TNF-alpha levels and lethality over a 48 h period in male CD-1 mice. The 5-lipoxygenase (LO) inhibitors, WY-50,295 tromethamine and zileuton (100 mg/kg p.o), significantly inhibited hypothermia at 4, 24 and 48 h after LPS. Interestingly, whereas cyclooxygenase (CO) inhibitors (ibuprofen, etodolac, naproxen and tenidap) at 40-80 mg/kg p.o. stimulated hypothermia at 4 h, they significantly reduced the later stages of hypothermia at 24-48 h. Rolipram (PDE-IV inhibitor) and dexamethasone significantly reduced hypothermia at 4-24 h and 1-24 h, respectively. All the anti-inflammatory agents significantly reduced elevated TNF-alpha levels at approximately 70 min post-LPS, except for ibuprofen. In conclusion, these anti-inflammatory standards indicate that LPS-induced shock involves multiple lipid mediators (PG's, LT's and possibly PAF) and secondary cytokine generation. This sublethal model of LPS-induced shock represents a sensitive model for estimating the efficacy of potential drug candidates for the treatment of endotoxic shock.
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PMID:Inhibition of endotoxin-induced hypothermia and serum TNF-alpha levels in CD-1 mice by various pharmacological agents. 827 85

At a subthermoneutral ambient temperature of 24 degrees C, intravenous administration of bacterial endotoxin (lipopolysaccharide, LPS) to rats resulted in hypothermia associated with a fall in oxygen consumption followed by fever. At the thermoneutral ambient temperature of 30 degrees C, animals only responded to LPS with fever. The hypothermia and reduction in oxygen consumption were attenuated in rats with eliminated peripheral macrophages. By contrast, macrophage elimination did not affect the febrile response to LPS. Both the hypothermia and the febrile response to LPS were prevented by peripheral administration of the cyclooxygenase inhibitor indomethacin. We conclude that hypothermia in response to LPS is caused by reduced thermogenesis, involves antipyretic products released from peripheral macrophages, and is mediated by prostaglandins. In addition, the febrile response likewise involves prostaglandins, but in contrast to the hypothermia appears to be independent of pyrogens released from peripheral macrophages. Previously, we reported the induction of the pyrogen interleukin-1 in the brain during the time course of the febrile response to LPS (34). The latter observations support the hypothesis that the second phase of biphasic fever is mediated by synthesis and action of pyrogens inside the blood-brain barrier.
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PMID:Hypothermia to endotoxin involves reduced thermogenesis, macrophage-dependent mechanisms, and prostaglandins. 830 29

Previously, we have reported that intravenous administration of bacterial endotoxin (lipopolysaccharide, LPS) in rats kept at a subthermoneutral ambient temperature of 24 degrees C results in a fall in colonic temperature that involved the release of antipyretic products by peripheral macrophages. Here, we demonstrate that treatment of rats with a biologically active antiserum to tumor necrosis factor (TNF) markedly attenuates the hypothermia in response to administration of LPS (0.5 mg/kg). Moreover, this hypothermia was prevented by central injection of a selective antagonist of V1 vasopressin receptors, dPTyr(Me) arginine vasopressin (AVP; 2 micrograms icv). AVP is thought to act as an antipyretic in the ventral septal area (VSA) of the brain. Because the AVP content of this area has been shown to be eliminated after long-term castration, we have tested the hypothesis that castration would attenuate the hypothermia in response to administration of LPS. Castrated rats displayed a markedly less hypothermic response than age-matched controls in response to administration of LPS. We conclude that hypothermia in response to intravenous injection of LPS involves the release of TNF from peripheral macrophages. Moreover, our results are consistent with the possibility that androgen-dependent vasopressinergic neurons in the VSA are mediating the hypothermia in response to intravenous administration of LPS.
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PMID:Hypothermia to endotoxin involves the cytokine tumor necrosis factor and the neuropeptide vasopressin in rats. 830 60

Because of its ability to efficiently inhibit in vitro cytokine production by activated macrophages, we hypothesized that interleukin (IL) 10 might be of particular interest in preventing endotoxin-induced toxicity. We therefore examined the effects of IL-10 administration before lipopolysaccharide (LPS) challenge in mice. A marked reduction in the amounts of LPS-induced tumor necrosis factor (TNF) release in the circulation was observed after IL-10 pretreatment at doses at low as 10 U. IL-10 also efficiently prevented the hypothermia generated by the injection of 100 micrograms LPS. Finally, pretreatment with a single injection of 1,000 U IL-10 completely prevented the mortality consecutive to the challenge with 500 micrograms LPS, a dose that was lethal in 50% of the control mice. We conclude that IL-10 inhibits in vivo TNF secretion and protects against the lethality of endotoxin in a murine model of septic shock.
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PMID:Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. 842 24

The studies were conducted on normal, febrile and cold-stressed rabbits. Fever was induced by a single intravenous injection of 1 micrograms/kg of E. coli lipopolysaccharide (LPS). The animals were submerged in ice-water for 20 s and then were kept at -15 degrees C for approx. 8 min., until their body temperature dropped by 3 degrees C. Sodium diethyldithiocarbamate (DTC) was injected i.v. to normal, febrile and cold-stressed rabbits, in a single dose of 2 or 20 mg/kg. The effect of DTC on body temperature, the number of neutrophils in blood, phagocytic activity of neutrophils and their ability to reduce nitroblue tetrazolium (NBT) were evaluated. It was found that DTC administered in a dose of 2 or 20 mg/kg did not affect the body temperature of rabbits. In normal rabbits, DTC did not change the number of neutrophils, but increased their phagocytic activity and ability to reduce NBT. In febrile rabbits, DTC depending on the dose, shortened the stimulating effect of LPS on neutrophil ability to reduce NBT but enhanced and prolonged the effect of pyrogen on neutrophil phagocytic activity. The rabbits treated with DTC prior to hypothermia exhibited shorter neutrophilia resulting from cold stress. In addition, DTC administered to the rabbits before their exposure to cold stress proved to be a partial or even total protection against the decrease in NBT reducing ability and phagocytic activity of blood neutrophils.
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PMID:Modulating effect of sodium diethyldithiocarbamate on neutrophils in normal, febrile and cold-stressed rabbits. 853 9

In the present study the regions of the brain showing an increase in the number of FOS protein stained cells 180 min following intravenous saline or bacterial lipopolysaccharide (LPS) treatment were investigated and correlated with changes in body temperature and plasma corticosterone levels. Particular attention was given to the possible involvement of the circumventricular organs and regions of the brainstem containing central noradrenergic neurones. LPS at doses of 0.35, 3.5 and 50 micrograms caused highly significant increases in FOS protein expression in the organum vasculosum of lamina terminalis, the area postrema and the subfornical organ compared with saline controls. Marked increases in bacterial lipopolysaccharide-induced FOS protein expression were observed in the ventrolateral medulla, the nucleus of the solitary tract and the locus coeruleus which contain the A1, A2 and A6 noradrenergic neurones respectively. The changes in body temperature induced by LPS were found to be dependent upon the dose of LPS administered; the lowest dose employed (0.35 micrograms) induced an immediate and sustained fever, 3.5 micrograms LPS caused a biphasic response consisting of a hypothermic response followed by a febrile response, whereas 50 micrograms LPS induced a hypothermic response which then normalised by 160 min post-injection. Intravenous saline injection had no significant effect on body temperature. The occurance of LPS-induced hypothermia was coincident with increased FOS expression in the bed nucleus of stria terminalis, which houses vasopressinergic neurones involved in antipyresis, whereas in animals showing an LPS-induced febrile response there was no significant difference in the number of FOS stained cells in the bed nucleus of stria terminalis compared with saline treated animals. LPS also caused marked increases in FOS protein expression in the parvocellular regions of the paraventricular nucleus (pPVN) of the hypothalamus, the central nucleus of the amygdala and the ventral septal area. Plasma corticosterone was unaffected by the lowest dose of LPS (0.35 micrograms), however the higher doses employed (3.5 and 50 micrograms) caused significant increases in plasma corticosterone which correlated with the increases in the number of FOS stained cells in the pPVN. The results of the present study suggest that, in addition to the organum vasculosum of lamina terminalis, the area postrema and subfornical organ may be important in the responses to antigenic challenge that are mediated by the central nervous system. They also add support to the possible involvement of the bed nucleus of stria terminalis in LPS-induced hypothermia and of the involvement of the of the major noradrenergic cell groups (A1, A2 & A6) and a number of hypothalamic and extrahypothalamic forebrain regions in the interaction of immune and central nervous systems.
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PMID:Bacterial lipopolysaccharide-induced changes in FOS protein expression in the rat brain: correlation with thermoregulatory changes and plasma corticosterone. 856 22

We hypothesized that the systemic inflammatory response undergoes two consecutive stages, each characterized by different nonspecific sickness patterns. To test this hypothesis, we studied thermal, nociceptive, and motor responses to lipopolysaccharide (LPS) in 43 unanesthetized, habituated, and lightly restrained male Wistar rats previously implanted with a catheter in the jugular vein. Escherichia coli LPS was injected intravenously in a dose of 0, 0.1, 1, 10, 100, or 1,000 micrograms/kg. Colonic temperature (Tc) was measured with a thermocouple. Changes in nociception were assessed by tail flick latency (TFL) to a noxious heat stimulus. Motor activity was evaluated using an observation-based activity score (AS). The two lowest doses were apyrogenic. The next dose induced a monophasic fever with a maximal Tc rise of 0.9 +/- 0.2 degrees C at 108 +/- 11 min post-LPS. The next two higher doses caused biphasic fevers with the first and second peaks of 0.7 +/- 0.1 and 1.4 +/- 0.1 degrees C (10 micrograms/kg) and 0.7 +/- 0.1 and 1.4 +/- 0.2 degrees C (100 micrograms/kg) occurring at 60 +/- 6 and 165 +/- 17 min and at 45 +/- 3 and 141 +/- 6 min, respectively. The highest dose of LPS resulted in a Tc fall (nadir, -0.6 +/- 0.1 degree C at 83 +/- 6 min). Two different sickness patterns were exhibited. The first (high Tc, low TFL and high AS) occurred during the monophasic fever and the first (early) phase of the biphasic fevers, and it was termed the early phase syndrome. The second pattern (high or low Tc, high TFL, and low AS) developed during the second (late) phase of the biphasic fevers and LPS-hypothermia (endotoxin shock), and it was termed the late phase syndrome. Occurring at different stages of the systemic inflammatory response and developing through different coping patterns [fight/flight (energy expenditure) vs. depression/withdrawal (energy conservation)], the two syndromes represent two different types of adaptation to infection and have different biological significance. Viewing sickness as a dynamic entity is justified clinically. Such a dynamic approach to the problem resolves several contradictions in the current concept of sickness.
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PMID:First and second phases of biphasic fever: two sequential stages of the sickness syndrome? 876 Feb 27

The labile gas nitric oxide (NO) mediates a wide variety of thermoregulatory processes including vasomotor control, brown fat thermogenesis, and neuroendocrine regulation. Additionally, during endotoxemia, NO modulates the release of cytokines and hypothalamic peptides. To determine the role of NO in thermoregulation and fever, we intravenously injected the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and measured its effects on body temperature during normal thermoregulation and endotoxemia in awake, unrestrained rats. L-NAME produced a stereoselective, dose-dependent hypothermia that lasted up to 4 h after bolus intravenous injection. Intravenous lipopolysaccharide (LPS) produced fever in a dose-dependent manner, which was preceded by hypothermia at higher doses alpha-LPS. NOS inhibition reduced the febrile response to LPS and produced marked hypothermia with a low dose of LPS. These findings indicate that NO may play an important role in thermoregulation and suggest that NO is required for the production of fever.
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PMID:Inhibition of nitric oxide synthase produces hypothermia and depresses lipopolysaccharide fever. 877 Jan 31


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