Divergent effects of brain interleukin-1ß in mediating fever, lethargy, anorexia and conditioned fear memory.

The influence of brain interleukin-1 (IL-1ß) on memory processes includes both detrimental and beneficial effects. To further explore the dynamics of brain IL-1ß in mediating learning and memory during acute sickness, we injected species-homologous rat IL-1ß (100ng/5μl) or vehicle (0.1% bovine serum albumin, 5μl) directly into the cisterna magna (i.

Simulated acute central Mycoplasma infections in rats induce fever, anorexia, body mass stunting and lethargy but spare memory.

Despite the documented post-infectious neurological complications of a central nervous system (CNS) Mycoplasma infection in humans, very few studies have investigated the acute inflammatory responses and sickness behaviours induced by CNS Mycoplasma infections. We therefore determined the effect of acute central administration of fibroblast-stimulating lipopeptide-1 (FSL-1), derived from Mycoplasma salivarium, and FAM-20 from a more pathogenic species, namely Mycoplasma pneumoniae, on behavioural and inflammatory responses in rats. Male Sprague-Dawley rats had radiotransmitters implanted, intra-abdominally, to measure body temperature and cage activity continuously.

Critical role for peripherally-derived interleukin-10 in mediating the thermoregulatory manifestations of fever and hypothermia in severe forms of lipopolysaccharide-induced inflammation.

Although peripherally released interleukin (IL)-10 has a critical regulatory role in limiting fever in mild-to-moderate forms of inflammation, its role in regulating the more complex thermoregulatory manifestations of hypothermia and fever noted during severe inflammation is less clear. Using cytokine antagonism, we therefore investigated the involvement of peripherally released IL-10 in mediating hypothermia, fever and inflammation induced by intraperitoneal (IP) administration of a large dose of lipopolysaccharide (LPS). Male Wistar rats (200-250 g) were anaesthetized and implanted intra-abdominally with temperature-sensitive radiotelemeters.

Simulated systemic recurrent Mycoplasma infection in rats induces recurrent sickness responses without residual impairment in spatial learning and memory.

In spite of their prevalence and importance, recurrent acute infections seldom have been investigated in the laboratory. We set out to measure fever and sickness behaviour in simulated recurrent Mycoplasma infection; Mycoplasma is a common clinical cause of recurrent acute infection. Male Sprague-Dawley rats had radiotransponders implanted to measure abdominal temperature and cage activity.

Dissociation between learning and memory impairment and other sickness behaviours during simulated Mycoplasma infection in rats.

To investigate potential consequences for learning and memory, we have simulated the effects of Mycoplasma infection, in rats, by administering fibroblast-stimulating lipopepide-1 (FSL-1), a pyrogenic moiety of Mycoplasma salivarium. We measured the effects on body temperature, cage activity, food intake, and on spatial learning and memory in a Morris Water Maze. Male Sprague-Dawley rats had radio transponders implanted to measure abdominal temperature and cage activity.

Differences in the relative involvement of peripherally released interleukin (IL)-6, brain IL-1β and prostanoids in mediating lipopolysaccharide-induced fever and sickness behavior.

Although peripherally released interleukin (IL)-6 is critical for fever, its role in sickness behaviors, in particular anorexia and lethargy, induced by lipopolysaccharide (LPS) administration appears to be less important. Using quantifiable measures of fever, anorexia and lethargy, that is, body temperature, food intake and voluntary wheel-running, we investigated whether the less-than-essential role for IL-6 in mediating sickness behaviors compared to fever implies important roles for other inflammatory mediators, particularly IL-1β and prostanoids, in these responses. Male Sprague-Dawley rats were randomly assigned to receive one of the following three injections before receiving a subcutaneous (SC) injection of LPS (250 μg/kg) or saline: (1) intraperitoneal injection of pre-immune serum or antiserum to IL-6 (IL-6AS), to reduce the biological activity of peripherally released IL-6; (2) intracerebroventricular injection of vehicle or a caspase-1 inhibitor, to inhibit the production of mature IL-1β; or (3) intraperitoneal injection of vehicle or one of the two doses (1 or 10 mg/kg) of diclofenac, a nonselective cyclooxygenase inhibitor shown to block the formation of prostanoids.

Interleukin (IL)-6 and IL-1 beta act synergistically within the brain to induce sickness behavior and fever in rats.

Pro-inflammatory cytokines interleukin (IL)-6 and IL-1 beta can act in the brain (centrally) to cause fever. Sickness behaviors which accompany fever also appear to involve the central action of IL-1 beta. We injected species-homologous rat IL-6 and IL-1 beta directly into the brains of conscious rats to examine the effect of these cytokines on fever, and two behaviors affected by sickness, voluntary wheel-running and food intake.

Growth failure after recurrent fever in young guinea pigs.

Infection causes fever and suppression of appetite, a combination of effects which threatens normal growth in infected children. We have used an animal model to study the effects on growth of recurrent simulated Gram-positive bacterial infection. After weaning, 10 guinea pig pups underwent surgery under general anaesthesia for the implantation of temperature-sensitive radiotelemeters and thereafter were assigned to receive intramuscular injections of either 50 microg/kg muramyl dipeptide (MDP), or sterile saline.

c-Fos immunoreactivity in selected brain regions of rats after heat exposure and pyrogen administration.

We determined c-Fos immunoreactivity (Fos-IR) in selected hypothalamic nuclei, the organum vasculosum of the laminae terminals (OVLT) and somatosensory cortex of rats after hyperthermia induced by exogenous heat exposure, Gram-negative or Gram-positive pyrogen administration. The magnitude of Fos-IR was similar in thermoregulatory hypothalamic nuclei of rats after heat exposure or lipopolysaccharide (LPS) injection, despite the different origins of the hyperthermias. Heat-induced hyperthermia was associated with increased Fos-IR in the somatosensory cortex.

Interleukin-6 and leptin mediate lipopolysaccharide-induced fever and sickness behavior.

Pro-inflammatory cytokines, interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) synthesized by activated macrophages and monocytes in response to administration of lipopolysaccharide (LPS), are considered important mediators of fever and sickness behavior. We administered rat-specific antisera for TNF-alpha, IL-1beta, IL-6 and leptin, to determine the involvement of peripherally released cytokines in LPS-induced fever and sickness behavior, measured as suppression of voluntary wheel-running and food intake. Male Sprague-Dawley rats (approximately 200 g) selected for their predisposition to spontaneously run on running wheels were anaesthetized with a combination of ketamine hydrochloride (80 mg/kg i.

Fever and lethargy induced by subcutaneous pyrogen infusion in unrestrained rats.

We have investigated the effects of continuous subcutaneous infusion of lipopolysaccharide (LPS), muramyldipeptide (MDP), or saline on abdominal temperature and voluntary activity in unrestrained rats. Both pyrogens were infused via osmotic pumps at a rate of approximately 2 microg.kg-1.

Inhibitors of nitric oxide synthesis block cold-induced thermogenesis in rats.

N-nitro-arginine methyl ester (L-NAME), an unspecific nitric oxide synthase inhibitor, was administered to individually caged Sprague-Dawley rats exposed to cold (18 degrees C) and thermoneutral (30 degrees C) environmental temperatures during the active phase of the animals' circadian cycle. Unrestrained rats were administered intraperitoneal injections of 100 mg x kg-1 L-NAME or 1 mL x kg-1 saline. Telemetry was used to measure abdominal temperature.

Effects of nitric oxide synthase inhibitors on the febrile response to muramyl dipeptide and lipopolysaccharide in rats.

We have administered aminoguanidine, a relatively specific inhibitor of inducible nitric oxide synthase, and N-nitro-L-arginine methyl ester (L-NAME), an unspecific nitric oxide synthase inhibitor, to rats made febrile with the gram-positive pyrogen, muramyl dipeptide and gram-negative pyrogen, lipopolysaccharide. Sprague-Dawley rats, housed individually at approximately 25 degrees C with a 12:12 h light:dark cycle (lights on 0700 hours), were injected (at 0900 hours) intraperitoneally with 50 mg/kg aminoguanidine, 25 mg/kg or 50 mg/kg L-NAME, and intramuscularly with 500 microg/kg muramyl dipeptide or 100 microg/kg lipopolysaccharide. Pyrogen injections were spaced at least 14 days apart.

Route of administration differentially affects fevers induced by Gram-negative and Gram-positive pyrogens in rabbits.

We have investigated the febrile responses of New Zealand White rabbits to a Gram-negative pyrogen (bacterial lipopolysaccharide (LPS) from Salmonella typhosa), commonly associated with systemic infection, and a Gram-positive pyrogen (Staphylococcus aureus), more frequently associated with superficial soft tissue infection, each administered via one of four different routes (intravenous, intramuscular, subcutaneous or intraperitoneal) at each of three different doses (LPS: 0.1, 1 and 10 microg kg(-1); S. aureus: 1.

Adaptive heterothermy and selective brain cooling in arid-zone mammals.

Adaptive heterothermy and selective brain cooling are regarded as important thermal adaptations of large arid-zone mammals. Adaptive heterothermy, a process which reduces evaporation by storing body heat, ought to be enhanced by ambient heat load and by water deficit, but most mammals studied fail to show at least one of those attributes. Selective brain cooling, the reduction of brain temperature below arterial blood temperature, is most evident in artiodactyls, which possess a carotid rete, and traditionally has been considered to protect the brain during hyperthermia.

Circadian variation in the effects of nitric oxide synthase inhibitors on body temperature, feeding and activity in rats.

We have investigated whether there is circadian variation in the effects of nitric oxide synthase inhibitors on body temperature, physical activity and feeding. We used nocturnally active Sprague-Dawley rats, housed at approximately 24 degrees C with a 12:12 h light:dark cycle (lights on 07:00 hours) and provided with food and water ad libitum. Nitric oxide synthesis was inhibited by intraperitoneal injection of the unspecific nitric oxide synthase inhibitor N-nitro- L-arginine methyl ester ( L-NAME, 100, 50, 25, 10 mg/kg), or the relatively selective inducible nitric oxide synthase inhibitor aminoguanidine (100, 50 mg/kg), during the day ( approximately 09:00 hours) or night ( approximately 21:00 hours).

Effects on fetal and maternal body temperatures of exposure of pregnant ewes to heat, cold, and exercise.

We exposed Dorper-cross ewes at approximately 120-135 days of gestation to a hot (40 degrees C, 60% relative humidity) and a cold (4 degrees C, 90% relative humidity) environment and to treadmill exercise (2.1 km/h, 5 degrees gradient) and measured fetal lamb and ewe body temperatures using previously implanted abdominal radiotelemeters. When ewes were exposed to 2 h of heat or 30 min of exercise, body temperature rose less in the fetus than in the mother, such that the difference between fetal and maternal body temperature, on average 0.

Feto-maternal relationships in goats during heat and cold exposure.

Maternal and fetal body temperatures were measured in five Boer goats, of mean mass 64 +/- 8 kg, using temperature-sensitive radiotelemeters implanted intra-abdominally. Body temperatures were recorded every 5 min. Throughout the last month of gestation, fetal temperature was approximately 0.

Fever and motor activity in rats following day and night injections of Staphylococcus aureus cell walls.

Body temperature and physical activity are affected by both circadian cycles and pyrogens. We injected intraperitoneally 2.5 x 10(9) cell walls of the gram-positive organism Staphylococcus aureus or sterile saline at three different times in the circadian temperature and activity rhythm of Sprague-Dawley rats.

The role of tumour necrosis factor-alpha (TNF-alpha) in fever and the acute phase reaction in rabbits.

We investigated the role of tumour necrosis factor-alpha (TNF-alpha) in fever and the acute phase reaction using a specific type-IV phosphodiesterase inhibitor, rolipram, that inhibits the production of TNF-alpha. The body temperatures and serum iron concentrations of rabbits were measured following injections of lipopolysaccharide (LPS) or Staphylococcus aureus (S. aureus) with either rolipram, diclofenac sodium or the appropriate control solutions.

Activity, blood temperature and brain temperature of free-ranging springbok.

We used miniature data loggers to record temperature and activity in free-ranging springbok (Antidorcas marsupialis) naturally exposed to severe nocturnal cold and moderate diurnal heat. The animals were active throughout the day and night, with short rests; the intensity of activity increased during daylight. Arterial blood temperature, averaged over many days, exhibited a circadian rhythm with amplitude < 1 degree C, but with a wide range which resulted from sporadic rapid deviations of body temperature.

Extracts of rhinoceros horn are not antipyretic in rabbits.

We administered extracts of the horn of the African Black rhinoceros intragastrically to 7 rabbits, at the same time as injecting bacterial lipopolysaccharide (LPS) intravenously into the rabbits to produce fever. At a dose of horn (50 mg/kg) similar to that allegedly used to reduce human fever, and at ten times that dose, the fever response to LPS was not significantly different (P > 0.05, t-test) to the response to LPS injection when boiled water was administered instead of horn extract.

Blood and brain temperatures of free-ranging black wildebeest in their natural environment.

Using miniature data loggers, we measured the temperatures of carotid blood and brain in four wildebeest (Connochaetes gnou) every 2 min for 3 wk and every 5 min, in two of the animals, for a further 6 wk. The animals ranged freely in their natural habitat, in which there was no shelter. They were subject to intense radiant heat (maximum approximately 1,000 W/m2) during the day.

Circulating cytokine concentrations and cytokine production by monocytes from newborn babies and adults.

As a possible factor responsible for reduced fever responses in the newborn, we measured plasma cytokine concentrations and cytokine production by neonatal monocytes after lipopolysaccharide or IL (interleukin)-1 alpha stimulation in vitro and compared these data with those obtained from adult plasma and monocytes. Whole blood was collected from afebrile adults (n = 12) and the umbilical cord of normal term infants (n = 12). Plasma and peripheral blood monocytes were prepared by conventional techniques.

Body temperatures of lambs and their mothers measured by radio-telemetry during parturition.

Using temperature-sensitive radio-telemeters chronically implanted in the abdomens of 8 fetal lambs and their mothers, we measured body temperature changes induced by parturition. Maternal body temperature rose at 0.70 +/- 0.