Drop In Body Temperature Research Articles

Establishment of antigen-specific IgE transgenic mice to study pathological and immunobiological roles of IgE in vivo

We have established transgenic mice that carry the genes coding for heavy and light chains of TNP-specific IgE. They produced high titers of TNP-specific IgE (20-40 microg/ml in serum) and their mast cells were heavily loaded with IgE. The level of FcepsilonRI expression on their mast cells was 6-8 times higher than that in non-transgenic littermates. The expression of low-affinity IgE receptor FcepsilonRII (CD23) on splenic B cells was also 6-8 times higher in the transgenic mice. Consistent with this, substantial amounts of IgE were detected on B cells in the transgenic mice. When challenged with i.v. administration of the corresponding antigen, the transgenic mice exhibited systemic anaphylactic symptoms such as a drastic drop of body temperature and extravasation of administered dye. Biphasic (immediate and delayed) ear swelling response was also elicited in a TNP-specific manner by epicutaneous antigen challenge without any prior sensitization. Thus, IgE produced in the transgenic mice was found to be biologically active to induce both local and systemic allergic reactions in vivo upon the challenge of the corresponding antigen. Taken together, the antigen-specific IgE transgenic mice established for the first time in this study appear to provide an attractive model system to study the pathological roles of IgE in acute and chronic phases of allergic inflammation as well as their immunobiological roles in vivo. They may also be useful to develop novel therapeutic strategies for atopic disorders.

In vitro binding and CNS effects of novel neurotensin agonists that cross the blood–brain barrier

Animal studies with neurotensin (NT) directly injected into brain suggest that it has pharmacological properties similar to those of antipsychotic drugs. Here, we present radioligand binding data for some novel hexapeptide analogs of NT(8-13) at the molecularly cloned rat and human neurotensin receptors (NTR-1), along with behavioral and physiological effects of several of these peptides after intraperitoneal (i.p.) administration in rats. One unique analog, NT66L, which had high affinity (0.85 nM) for the molecularly cloned rat neurotensin receptor (NTR-1), caused a drop in body temperature and antinociception at doses as low as 0.1 mg/kg after i.p. injection. At 30 min post-injection, the ED 50 for NT66L-induced hypothermia (rectal temperature) and antinociception (hot plate test) was 0.5 and 0.07 mg/kg, respectively. At a dose of 1 mg/kg i.p., NT66L caused 100% of the maximum possible effect for antinociception for up to 2 h after administration. At this dose body temperature lowering was greater than −2.5°C from 20 to 120 min after i.p. administration. These results in animals suggest that NT66L has agonist properties at NTR-1 in vivo after extracranial administration and provide support for its further study in behavioral tests predictive of neuroleptic activity.

Oral Antibiotics reduce Body Temperature of Healthy Rabbits in a Thermoneutral Environment

Nonabsorbable oral antibiotics, which reduce gut flora, decrease the daytime and night-time body temperatures of rats and mice. We investigated whether oral antibiotics would also lower the body temperature of healthy rabbits. Six rabbits received neomycin sulphate in their drinking water for ten days, and seven rabbits received a mixture of chloramphenicol and dihydroxystreptomycin for six days. Body temperatures, recorded using intra-abdominal radiotelemeters, decreased significantly, by 0.2-0.3 degree C, after three days of antibiotic treatment in both groups of rabbits. The drop in body temperature was transient; after six days body temperatures returned to pre-antibiotic levels. Antibiotic treatment had no effect on either the acrophase or the amplitude of the circadian rhythm in body temperature. Oral antibiotics therefore reduce body temperature of rabbits, without influencing the circadian rhythm in body temperature. Our results are consistent with the hypothesis that an agent arising from intestinal bacteria sustains an elevated body temperature in healthy animals.

Effects of Fasting on the Circadian Body Temperature Rhythm of Japanese Quail

The effect of food deprivation on the body temperature and activity rhythms of quail was assessed in birds exposed to both light–dark (LD) cycles and to continuous darkness (DD). Quail normally exhibit a daily rhythm of body temperature in LD that will persist in DD (that is, the rhythm is circadian). In LD, 3 days’ food deprivation caused the body temperature to drop below its normal nighttime levels, whereas daytime body temperature was unaffected. In DD, food deprivation caused the body temperature to drop below normal at all phases of the circadian rhythm of body temperature. Accordingly, the lack of hypothermia during the light phase of the LD cycle following food deprivation must represent a direct exogenous or “masking” effect of light, and is not an endogenous property of the circadian system. Blind birds exposed to LD 12:12 exhibited an entrained body temperature rhythm, and food deprivation caused a drop in body temperature below normal levels during both the light and dark phases of the LD cycle. Accordingly, the masking effects of light observed in normal birds on LD cycles is mediated via retinal photoreceptors and not via extraretinal photoreceptors. Measurements of activity levels before and during fasting indicate that fasting-induced hypothermia cannot be explained simply as a consequence of decreases in activity levels. Food deprivation was also observed to cause significant phase shifts in the endogenous rhythm of body temperature.

Toxicity of hercides 2,4-D and MCPA for Rats and Rabbits

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Hypophagia-induced hypometabolism during experimental anaemia in rats

Several investigators have reported a drop in oxygen (O2) consumption (VO2) and body temperature in laboratory animals during normobaric or hypobaric hypoxia. Hypophagia, with normal efficiency of protein utilisation for growth, was also observed. It has recently also been observed that hypometabolism is present during anaemic hypoxia. The present study was designed to test the experimental hypothesis that anaemic hypoxia induces hypometabolism secondary to hypophagia. Episodes of anaemia were created in adult male rats by either blood withdrawal through cardiac puncture (haemorrhagic anaemia) or phenylhydrazine administration (haemolytic anaemia). Haematrocrit, VO2, and food consumption, as indirect estimations of the level of anaemia, energy production, and appetite, respectively, were serially measured in all animals during 7 days (acute experiments) or 17 days (chronic experiments). Positive correlations were found between the three parameters during development of and recovery from anaemia during each anaemic episode. When the amount of food offered to non-anaemic rats was equalised to that freely eaten by anaemic rats, VO2 dropped in the former to almost the level found in the latter. Body composition changed during chronic anaemia because of a decrease in the lipid fraction of the body. The results confirmed the working hypothesis that hypometabolism, which has been considered as an immediate, emergency-type response to both hypoxic and anaemic hypoxia, can be considered as a response secondary to hypophagia because of depressed appetite. How appetite is adapted to the mechanisms which control O2 convection and O2 availability is not known at present.

Effect of nitric oxide synthase inhibition on hypercapnia-induced hypothermia and hyperventilation.

Hypercapnia elicits hypothermia in a number of vertebrates, but the mechanisms involved are not well understood. In the present study, we assessed the participation of the nitric oxide (NO) pathway in hypercapnia-induced hypothermia and hyperventilation by means of NO synthase inhibition by using Nomega-nitro-L-arginine (L-NNA). Measurements of ventilation, body temperature, and oxygen consumption were performed in awake unrestrained rats before and after L-NNA injection (intraperitoneally) and L-NNA injection followed by hypercapnia (5% CO2). Control animals received saline injections. L-NNA altered the breathing pattern during the control situation but not during hypercapnia. A significant (P < 0.05) drop in body temperature was measured after both L-NNA (40 mg/kg) and 5% inspired CO2, with a drop in oxygen consumption in the first situation but not in the second. Hypercapnia had no effect on L-NNA-induced hypothermia. The ventilatory response to hypercapnia was not changed by L-NNA, even though L-NNA caused a drop in body temperature. The present data indicate that the two responses elicited by hypercapnia, i.e., hyperventilation and hypothermia, do not share NO as a common mediator. However, the L-arginine-NO pathway participates, although in an unrelated way, in respiratory function and thermoregulation.

Role of mast cells and monoamines in the thrombocytopaenia and mortality elicited by tumour necrosis factor in mice.

We explored the thrombocytopaenia elicited by the i.v. injection of mouse recombinant tumour necrosis factor (TNF) in mice. Injection of 10 micrograms of TNF led to a thrombocytopaenia (evident after 0.5 hr) which was caused by decreased platelet survival, as seen by the injection of labelled platelets. TNF-induced thrombocytopaenia was not prevented by heparin, nor by depletion of either fibrinogen or C'. TNF-induced thrombocytopaenia was markedly attenuated in mice treated with reserpine, an agent that depletes monoamines from mast cells and other cells, and in the mast-cell-deficient WWv mice. In vitro, TNF elicited a modest release of monoamine from peritoneal mast cells and from a mast cell line. When mice are injected with 3H-serotonin (3H-5HT) before TNF, TNF injection increased the plasma 3H-5HT content 1 hr later, modifications absent in reserpine pretreated or mast-cell-deficient mice. 3H-5HT content of the small intestine was markedly depleted in TNF-injected mice, suggesting that this organ is the source of the plasma 3H-5HT. Drop in body temperature and mortality induced by TNF were also attenuated in mast-cell-deficient, and in reserpine pretreated mice. These results indicate that TNF can induce a release of monoamines from mast cells, mainly from those of the small intestine, a process that contributes to TNF-induced thrombocytopaenia and mortality.

Hypoxia inhibits cold-induced huddling in rat pups

We asked to what extent hypoxia would modify the huddling behaviour of young rats during cold exposure. Sets of five animals (postnatal age 9±1 days) were placed at predetermined positions in a chamber maintained at ∼33°C (warm) or ∼15°C (cold), in normoxia or hypoxia (10% inspired O 2), and their movements monitored for 30 min by a video camera. The surface areas (SA) of each individual pup (SAi) and of the whole set of pups (SAset) was measured every 5 min. In warm, the rats spread out, and both SAi and SAset were the greatest, whether in normoxia or hypoxia. In hypoxia, the total travelled distance (TTD) was much greater than in normoxia. In cold, during normoxia, SAi and SAset were decreased because of postural changes and huddling, and body temperature, measured at the end of the exposure, was also decreased. In hypoxic-cold, compared to normoxic-cold, fewer pups were in contact with one another, SAi and SAset did not decrease and the drop in body temperature was larger. Differently from hypoxia, hypercapnia (5% CO 2) did not modify the responses observed during breathing air, whether in warm or cold conditions. We conclude that hypoxia, in addition to inhibiting shivering and non-shivering thermogenesis, can also limit behavioural thermogenesis, with the effect of further lowering body temperature.

Ethanol-Induced Hypothermia and Thermogenesis of Brown Adipose Tissue in the Rat

The effects of two ethanol doses (2 and 3 g/kg) on colonic temperature and levels of norepinephrine (NE) and uncoupling protein (UCP) mRNA in the interscapular brown adipose tissue (IBAT) were examined in rats exposed to 20°C or 4°C for 2 h. The controls received 0.9% NaCl solution. Ethanol produced a significant hypothermic effect versus saline at both temperature conditions. The dose at 3 g/kg reduced colonic temperature more in the cold than at room temperature ( p < 0.01), whereas the ambient temperature did not affect the decrease in rats that received ethanol 2 g/kg. At room temperature ethanol did not significantly change the levels of NE or UCP mRNA, whereas after cold exposure (4°C) NE levels in the ethanol-treated rats were significantly lower than in the controls ( p < 0.001). Ethanol did not prevent a cold-induced increase in the UCP mRNA levels, although it reduced an increase. The magnitude of the reduction in increase was dependent on the dose, being significant at the dose of 3 g/kg ( p < 0.05). The results show that the ethanol-induced drop in body temperature is not necessarily related to IBAT thermogenesis, as indicated by the levels of NE and UCP mRNA.

Physiological significance of behavioral hypothermia in hypoglycemic frogs ( Rana catesbeiana)

Hypoxia elicits a number of compensatory responses in animals, including behavioral hypothermia. The hypothesis that hypoglycemia induces hypothermia in the bullfrog Rana catesbeiana was tested and that this behavioral response would be beneficial. Frogs equipped with a temperature probe were tested in a thermal gradient (10–40°C). Insulin (15 IU kg −1) caused significant reduction of body temperature, from 25.0 to 17.8°C. A non-metabolizable glucose analogue, 2-deoxy- d-glucose (2-DG, 50 mg kg −1),which blocks intracellular glucose utilization, was also injected and caused a similar drop in body temperature, despite an increase in plasma glucose levels. To assess the possible benefits of hypoglycemia-induced hypothermia, the effects of insulin and 2-DG injections were measured on plasma glucose concentration and on oxygen consumption of frogs equilibrated at 10, 20 and 30°C. The plasma glucose was elevated at higher temperatures and so was oxygen consumption. The insulin caused a significant reduction of plasma glucose concentration (about 1.22 μMol ml −1) whereas 2-DG caused a significant increase (about 0.70 μMol ml −1) at 30°C. Both drugs caused a reduction of oxygen consumption (approximately 0.388 and 0.382 ml min −1 kg at 30°C after insulin and 2-DG injection, respectively). No effect of either insulin or 2-DG was observed when the animals were equilibrated at 10°C. In conclusion, hypothermia may be a beneficial response to hypoglycemia in frogs.

Effects of 2-deoxy-D-glucose and insulin on plasma glucose levels and behavioral thermoregulation of toads.

The present study was designed to test the hypothesis that hypoglycemia induces hypothermia in ectotherms and to elucidate the mechanisms responsible for behavioral hypothermia. Behavioral hypothermia is a stress response that occurs in organisms ranging from protozoans to mammals, but very little is known about the cellular mechanisms involved. Toads equipped with a temperature probe were tested in a thermal gradient (10-40 degrees C). Insulin was used to reduce plasma glucose levels, and an inhibitor of glucose utilization, 2-deoxy-D-glucose (2-DG), was used to cause intracellular glucopenia. Insulin injections into the dorsal lymph sac caused significant reductions of both plasma glucose levels and body temperature. To determine if the response was mediated by extracellular glucose receptors or an intracellular mechanism. 2-DG was also injected into the lymph sac. 2-DG caused a similar drop in body temperature and a marked increase in plasma glucose. To assess the role of central thermoregulatory mechanisms, a smaller dose of 2-DG was injected into the fourth cerebral ventricle or the lymph sac. Intracerebroventricular injection of 2-DG caused a decrease in body temperature despite elevated circulating glucose levels, whereas injection into the lymph sac caused no significant change. The data indicate that exclusion of glucose from central rather than peripheral sites plays a major role in the hypoglycemia-induced behavioral hypothermia and that intracellular mechanisms rather than extracellular glucose receptors are involved in this response. Hypothermia may be a beneficial response to hypoglycemia in toads because it dampens cellular oxidative demands during glucose deprivation.

Field immobilization of muskrats (Ondatra zibethicus) for minor surgical procedures.

A combination of ketamine hydrochloride and xylazine hydrochloride at doses of 50 mg/kg and 5 mg/kg, respectively, was used to immobilize 48 muskrats (Ondatra zibethicus) from October 1993 to November 1994 in Tennessee (USA). Mean (+/-SD) time for induction was 2.97 +/- 1.1 min. After a mean (+/-SD) duration of 27.2 +/- 3.5 min intramuscular yohimbine hydrochloride at a dose of 0.125 mg/kg was administered. Mean (+/-SD) recovery time was 48.1 +/- 21.6 min. All anesthetic inductions were smooth and sufficient depth of anesthesia was achieved to allow surgical collection of adipose tissue. Recovery times were more variable than expected. There was a significant (P < or = 0.05) drop in heart rate, respiratory rate, and body temperature during anesthesia. One animal died during recovery.

Alpha1-Antitrypsin inhibits the lethal response to TNF in mice.

alpha1-Antitrypsin, an acute-phase reactant in many species, protects significantly against the lethality induced by TNF or endotoxin in mice. The protection is optimal with a single dose of at least 300 microg i.p. or 100 microg i.v. given 2 h before a lethal challenge, either with a low dose of TNF in the presence of galactosamine or a higher dose of murine TNF alone. Under optimal conditions, the drop in body temperature, the release of liver transaminases, and the increase in clotting time are also inhibited. alpha1-Antitrypsin does not protect against a lethal dose of platelet-activating factor. It is suggested that the protection is due to reduced release of platelet-activating factor.

Grooming secretions and seasonal adaptations in the blind mole rat ( Spalax ehrenbergi)

The postulated thermoregulatory function of grooming in the “blind” mole rat ( Spalax ehrenbergi), a solitary, highly aggressive subterranean rodent, was tested by subjecting individuals to extreme hot and cold environments and measuring their grooming frequency and thermoregulatory capacity. It was found that exposure to heat stress during both the winter and the summer failed to elicit grooming in isolated mole rats, even though their body temperature was significantly elevated. Thus, unlike Mongolian gerbils ( Meriones unguiculatus), mole rats do not seem to have a mechanism for lowering body temperature by grooming. However, at low temperatures, grooming behavior significantly increased during both seasons, although a decline in body temperature was recorded only during the summer. Because grooming in mole rats expresses Harderian lipids onto the fur, it is suggested that in the winter, under cold stress, this behavior might prevent a drop in body temperature through spreading insulating Harderian lipids.

The effect of He?O2 exposure on metabolic rate, thermoregulation and thermal conductance during normothermia and daily torpor

Recently it was proposed that the low metabolic rate during torpor may be better explained by the reduction of thermal conductance than the drop of body temperature or metabolic inhibition. We tested this hypothesis by simultaneously measuring body temperature and metabolic rate as a function of ambient temperature in both torpid and normothermic stripe-faced dunnarts, Sminthopsis macroura (Marsupialia; approx. 25 g body mass), exposed to either air or He−O2 (21% oxygen in helium) atmospheres. He−O2 exposure increases the thermal conductance of homeothermic mammals by about twofold in comparison to an air atmosphere without apparent side-effects. Normothermic S. macroura exposed to He−O2 increased resting metabolic rate by about twofold in comparison to that in air because of the twofold increase in apparent thermal conductance. Torpid S. macroura exposed to He−O2 at ambient temperatures above the set-point for body temperature showed a completely different metabolic response. In contrast to normothermic individuals, torpid individuals significantly decreased or maintained a similar metabolic rate as those in air although the apparent thermal conductance in He−O2 was slightly raised. Moreover, the metabolic rate during torpor was only a fraction of that of normothermic individuals although the apparent thermal conductance differed only marginally between normothermia and torpor. Our study shows that a low thermal conductance is not the reason for the low metabolic rates during torpor. It suggests that interrelations between metabolic rate and body temperature of torpid endotherms above the set-point for body temperature differ fundamentally from those of normothermic and homeothermic endotherms.

Dysregulation of Temperature and Liver Cytokine Gene Expression in Immunodeficient Wasted Mice

Wasted mice bear the spontaneous autosomal recessive mutationwst/wst;this genotype is associated with weight loss beginning at 21 days of age, neurologic dysfunction, immunodeficiency at mucosal sites, and increased sensitivity to the killing effects of ionizing radiation. The pathology underlying the disease symptoms is unknown. Experiments reported here were designed to examine thermoregulation and liver expression of specific cytokines in wasted mice and in littermate and parental controls. Our experiments found that wasted mice begin to show a drop in body temperature at 21–23 days following birth, continuing until death at the age of 28 days. Concomitant with that, livers from wasted mice expressed increased amounts of mRNAs specific for cytokines IL-6 and IL-1, the acute phase reactant C-reactive protein, c-jun,and apoptosis-associated Rp-8 when compared to littermate and parental control animals. Levels of β-transforming growth factor, c-fos,proliferating cell nuclear antigen, and ornithine amino transferase transcripts were the same in livers from wasted mice and controls. These results suggest a relationship between an acute phase reactant response in wasted mice and temperature dysregulation.

A short red light pulse during dark phase of LD-cycle perturbs the hamster's circadian clock.

In this study we investigated the influence of red light< which naturally occurs during dawn and dusk, on locomotor activity and body temperature rhythms of Djungarian hamsters (Phodopus sungarus). A single weak red light pulse given 2 h before regular lights on had acute as well as long-term effects persisting for several days following exposure. The hamsters immediately stopped their locomotor activity, accompanied by a drop in body temperature. In the following undisturbed nights (ID 16:8) the nocturnal activity stopped earlier than usual. This lasting effect of the light pulse was more pronounced than the acute effect. The activity phase compressed gradually during 3 to 5 days after the light pulse was administered while time of activity onset was almost unaffected. It took 6 to 11 days for complete recovery of the original activity phase. The maximal activity compression and the recovery period depended on the duration of the single red light pulse and its intensity. Red light pulses of 15 min duration were about twice effective as 1 min pulses; and the effect of a red light pulse of 130 mW/m2 was about 1.5 times stronger than a 30 mW/m2 red light pulse. The maximal value of activity phase compression reached in this experiment was 2.5 + 0.2 h with a recovery period of 11.1 +/- 0.3 days following a given red light pulse of 90 mW/m2 and 15 min. The "morning oscillator" seems to be persistently affected. This indicates a very high photosensitivity of the Djungarian hamster's circadian system to red light.

Ventilatory and metabolic responses to hypoxia during moderate hypothermia in anesthetized rats

In resting euthermic mammals, hypoxia elicits a hyperventilation that results from a combination of hyperpnea and hypometabolism. Often accompanying the hypoxia-induced hypometabolism is a drop in body temperature. To separate the synergic effects of hypothermia per se from the direct effects of hypoxia on metabolic rate, ventilation (VE), and O2 consumption (VO2) were measured in anesthetized rats fitted with abdominal heat exchangers and maintained at either normothermic (37.5 degrees C) or hypothermic (35 degrees C) body temperatures while exposed to either normoxia or hypoxia (7% O2). Hypothermia induced parallel decreases in VE and VO2, thereby maintaining VE/VO2. Hypoxia resulted in a hyperventilation achieved with the same relative decrease in VO2 and increase in VE in both normothermic and hypothermic rats. The results suggest that 1) the changes in metabolic rate and VE during hypothermia reflect a direct effect of cold and, 2) because of similar levels of hypoxic hyperventilation in the hypothermic and normothermic rats, relative to metabolic rate, respiratory gain has not been depressed in hypothermic rats.

Hypothermia markers: serum, urine and adrenal gland catecholamines in hypothermic rats given ethanol

The effect of ethanol (2 g/kg) on body temperature and catecholamine (CA) secretion in the cold (−20 °C) was investigated in adult male and female rats. The temperature dropped more rapidly in the females, being ~ 10 °C after 3 h as compared with 18 °C in the males. Controls received the same dose of ethanol but were kept at +20 °C. Increased concentrations of adrenaline (A) and noradrenaline (NA) were already observed in the serum and urine of the females after 0.5 h of exposure, but at 1 h in the males. Serum values were low in the females after 2 and 3 h and urine values high in connection with the deep hypothermic state. The urine values of the males were also high at the end of exposure, when they, too, were hypothermic. Depletion of amines was observed in the adrenals during the hypothermia phase, while CA concentrations tended to rise in the serum of the rats kept in the warm. The CA index (A:NA) was generally > 1 in both the serum and urine of the cold-exposed rats. The results show that female rats are less resistant to hypothermia than males, as indicated by their more rapid drop in body temperature and exhaustion of CA secretion. It is also apparent that urine CAs are worth measuring in cases of accidental hypothermia and possibly also other types of stress. An elevated CA index (> 1) seems to be an additional marker of hypothermia, showing a proportionally greater increase in the secretion of A than NA during cold stress.