Biphasic fever: what triggers the second temperature rise?

1995 ◽  
Vol 269 (2) ◽  
pp. R280-R286 ◽  
Author(s):  
A. A. Romanovsky ◽  
C. M. Blatteis
Keyword(s):  
Body Temperature ◽  
Temperature Rise ◽  
Guinea Pigs ◽  
Direct Consequence ◽  
Second Phase ◽  
Febrile Response ◽  
Intravenous Catheters ◽  
Second Peak

The mechanism of initiation of the second body temperature (Tb) rise of the typically biphasic lipopolysaccharide (LPS) fever is not known. This study was undertaken to test the hypothesis that the second Tb rise during fever may be initiated as a direct consequence of the elevated Tb of the first febrile rise. Experiments were conducted in conscious guinea pigs implanted with intraperitoneal thermodes, intravenous catheters, and intrahypothalamic thermocouples. Intraperitoneal cooling (IPC) was performed by perfusing water (22 degrees C) through the thermode under afebrile conditions during the first (0-40 min after pyrogen injection) or second (80-120 min) phase of the biphasic LPS (2 g/kg iv) fever or during a monophasic LPS (0.5 g/kg iv) fever. Throughout IPC, the rate of heat withdrawal was maintained at 11.6 +/- 1.2 mW/g. No IPC was performed in the corresponding controls. When started immediately after LPS administration at the higher dose, IPC completely blocked the first phase of the biphasic fever. This blockade was followed by a Tb rise, which, although similar to the rise in the second phase, might alternatively be interpreted as the delayed occurrence of the first phase previously suppressed by IPC. However, we excluded the later possibility by showing the absence of an overshoot in Tb restoration after IPC applied during the second phase of biphasic fever, during monophasic fever, or under afebrile conditions. We conclude, therefore, that the second Tb rise of biphasic LPS fever is not induced by the elevated Tb of the first febrile phase. The cause of the second peak of the characteristic biphasic febrile response to intravenous LPS remains speculative.

Kinetics of systemic and intrahypothalamic IL-6 and tumor necrosis factor during endotoxin fever in guinea pigs

1993 ◽  
Vol 265 (3) ◽  
pp. R653-R658 ◽  
Author(s):  
J. Roth ◽  
C. A. Conn ◽  
M. J. Kluger ◽  
E. Zeisberger
Keyword(s):  
Body Temperature ◽  
Tumor Necrosis Factor ◽  
Guinea Pigs ◽  
Tumor Necrosis ◽  
Time Course ◽  
Clear Correlation ◽  
Febrile Response ◽  
Fever Response ◽  
Kinetics Of ◽  
Necrosis Factor

The time course of activity of interleukin-6 (IL-6) and tumor necrosis factor (TNF) was measured in blood plasma and hypothalamic push-pull perfusates during the febrile response to intramuscular injection of bacterial endotoxin (Escherichia coli, 20 micrograms/kg) in 24 guinea pigs. Injection of endotoxin caused a dramatic increase of IL-6 activity in plasma. The logarithmic values of plasma IL-6 activities showed a linear correlation to the febrile change in body temperature (r = 0.898) during the whole time course of fever. IL-6 activity in hypothalamic perfusates increased 12-fold in the first hour after pyrogen application and declined slowly despite the further increase in body temperature. Hypothalamic IL-6 activity did not correlate with the febrile increase in body temperature (r = -0.048). TNF activity in plasma, not detectable before pyrogen application, had its peak in the first hour after endotoxin injection and rapidly declined to 15-20% of the peak activity within the next 2 h and to an undetectable value 5 h after injection. In the hypothalamus TNF was not detectable before endotoxin injection, but it could be monitored in most animals after pyrogen application without a clear correlation to the fever response. These results taken together indicate that endotoxin fever represents a physiological situation in which production and release of cytokines in the peripheral immune system and in the hypothalamus are regulated and stimulated in independent patterns.

Interaction between norepinephrine and prostaglandin E2 in the preoptic area of guinea pigs

1996 ◽  
Vol 271 (3) ◽  
pp. R528-R536 ◽  
Author(s):  
E. Sehic ◽  
A. L. Ungar ◽  
C. M. Blatteis
Keyword(s):  
Cerebrospinal Fluid ◽  
Body Temperature ◽  
Prostaglandin E2 ◽  
Intravenous Injection ◽  
Guinea Pigs ◽  
Preoptic Area ◽  
Extracellular Fluid ◽  
Low Ph ◽  
Febrile Response ◽  
Artificial Cerebrospinal Fluid

The release of norepinephrine (NE) and prostaglandin E2 (PGE2) in the preoptic-anterior hypothalamus (POA) by systemically administered pyrogens suggests that both substances may mediate the febrile response. To investigate their possible interaction, we measured directly the levels of PGE2 in the extracellular fluid of the POA of conscious guinea pigs microdialyzed intrapreoptically with exogenous NE over the entire course of their febrile response to endotoxin. Acidified and buffered NE (NEa, NEb), artificial cerebrospinal fluid (aCSFa, aCSFb), and vehicle (Veha, Vehb) were tested. All but aCSFb depressed the febrile response to endotoxin. The microdialysis of aCSFa, aCSFb, Veha, Vehb, and NEa did not change basal preoptic PGE2 levels. However, NEb, at a dose that by itself did not affect body temperature (Tb), caused a large elevation in preoptic PGE2. The intravenous injection of endotoxin increased the level of PGE2 in the POA. NEb potentiated this increase, whereas NEa, aCSFa, and Vehb reduced it; Veha reduced it for the first 60 min and enhanced it for the last 90 min of the experiment. Thus these data suggest that the low pH of the NE solute and/or its Veh may confound the observed effects of NE on the Tb and preoptic PGE2 induced by endotoxin. We surmise that this is due to a neurotoxic action of the antioxidants and the acidity of the solution on thermosensitive neurons in the POA. Hence, the results of experiments using exogenous, usually acidified, NE preparations that often also contain additives should be interpreted with caution.

Repeated infusions of TNF-alpha cause attenuation of the thermal response and influence LPS fever in guinea pigs

1996 ◽  
Vol 270 (4) ◽  
pp. R749-R754 ◽  
Author(s):  
J. M. Goldbach ◽  
J. Roth ◽  
B. Storr ◽  
E. Zeisberger
Keyword(s):  
Guinea Pigs ◽  
Thermal Response ◽  
Repeated Administration ◽  
Tnf Alpha ◽  
Control Group ◽  
Second Phase ◽  
Febrile Response ◽  
Lower Reactivity ◽  
Freely Moving ◽  
Necrosis Factor

In conscious, freely moving guinea pigs, tumor necrosis factor (TNF)-alpha and TNF-beta, infused into the aortic arch within a period of 45 min at a dosage of 5 micrograms/kg, induced different thermal responses. TNF-alpha evoked a biphasic elevation of abdominal temperature, both phases together lasting longer than 6 h. In response to infusions of TNF-beta, the first phase, lasting approximately 120 min, was the same as was observed in response to TNF-alpha, whereas the longer second phase of temperature increase was missing. When the infusion of TNF-alpha was repeated four times at intervals of 3 days, the second phase of the increase in abdominal temperature (120-360 min after start of infusion) tended to decrease in response to the third and was significantly attenuated in response to the fourth infusion of TNF-alpha. A control group of guinea pigs received four infusions of solvent (0.9% sterile pyrogen-free saline). Another 3 days after the fourth infusion of TNF-alpha or solvent, all animals were injected with 20 micrograms/kg bacterial lipopolysaccharide (LPS from Escherichia coli; intramuscular injection). In those guinea pigs having developed a reduced responsiveness to TNF-alpha, the first phase of LPS-induced fever was significantly suppressed, whereas the second phase tended to be enhanced, compared with animals having received four infusions of solvent. In conclusion, guinea pigs develop a reduced responsiveness to TNF-alpha after its repeated administration. In the state of lower reactivity to exogenous TNF-alpha, a reduced response of the first phase of LPS-induced fever (during which endogenous TNF-alpha is released) can be observed. This indicates that endogenous TNF-alpha may contribute to LPS-induced fever only in the initial phase of the febrile response of guinea pigs.

Febrile and metabolic tolerance to endotoxin and human recombinant interleukin-1 beta in rabbits

1993 ◽  
Vol 264 (6) ◽  
pp. R1180-R1185 ◽  
Author(s):  
O. Yamashiro ◽  
A. Morimoto ◽  
Y. Sakata ◽  
T. Watanabe ◽  
N. Murakami
Keyword(s):  
Leukocyte Count ◽  
Interleukin 1 ◽  
Metabolic Responses ◽  
Second Phase ◽  
Interleukin 1 Beta ◽  
Plasma Zinc ◽  
Febrile Response ◽  
Intravenous Injections ◽  
Intracerebroventricular Injections ◽  
Second Peak

We investigated whether or not tolerance of the febrile and metabolic responses to human recombinant interleukin-1 beta (IL-1 beta) develops in rabbits. Febrile tolerance to bacterial endotoxin was induced by daily injections of lipopolysaccharide (LPS, 5.0 micrograms/kg iv). In LPS-tolerant rabbits, the second phase of the biphasic fever induced by intravenous injections of LPS (5.0 micrograms/kg) or IL-1 beta (2.0 micrograms/kg) was significantly reduced. However, the first phase was almost the same as that observed in normal rabbits. Five daily injections of IL-1 beta (2.0 micrograms/kg iv) resulted in the development of tolerance of the febrile response to IL-1 beta. In IL-1 beta-tolerant rabbits, the second peak of the biphasic fever was significantly reduced. In addition, decreases in leukocyte count and plasma zinc induced by intravenous injections of LPS or IL-1 beta were significantly reduced in LPS- or IL-1 beta-tolerant rabbits. However the monophasic fever induced by a smaller dose of IL-1 beta (0.5 microgram/kg iv) and the first peak of the IL-1 biphasic fever were almost the same as those observed in normal rabbits. Febrile responses induced in LPS- or IL-1 beta-tolerant rabbits by intracerebroventricular injections of LPS (5.0 ng) or IL-1 beta (2.0 ng) were similar to those observed in normal rabbits. The present results suggest that tolerance of the febrile and metabolic responses to IL-1 beta is developed after repeated injections of IL-1 beta and that reduced responsiveness to IL-1 beta is partly involved in the development of LPS tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Pathophysiology of Fever and Application of Infrared Thermography (IRT) in the Detection of Sick Domestic Animals: Recent Advances

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2316
Author(s):  
Daniel Mota-Rojas ◽  
Dehua Wang ◽  
Cristiane Gonçalves Titto ◽  
Jocelyn Gómez-Prado ◽  
Verónica Carvajal-de la Fuente ◽  
...  
Keyword(s):  
Body Temperature ◽  
Infrared Thermography ◽  
Core Body Temperature ◽  
The Body ◽  
Farm Animals ◽  
Economic Losses ◽  
Febrile Response ◽  
Temperature Range ◽  
Stable Temperature ◽  
Core Body

Body-temperature elevations are multifactorial in origin and classified as hyperthermia as a rise in temperature due to alterations in the thermoregulation mechanism; the body loses the ability to control or regulate body temperature. In contrast, fever is a controlled state, since the body adjusts its stable temperature range to increase body temperature without losing the thermoregulation capacity. Fever refers to an acute phase response that confers a survival benefit on the body, raising core body temperature during infection or systemic inflammation processes to reduce the survival and proliferation of infectious pathogens by altering temperature, restriction of essential nutrients, and the activation of an immune reaction. However, once the infection resolves, the febrile response must be tightly regulated to avoid excessive tissue damage. During fever, neurological, endocrine, immunological, and metabolic changes occur that cause an increase in the stable temperature range, which allows the core body temperature to be considerably increased to stop the invasion of the offending agent and restrict the damage to the organism. There are different metabolic mechanisms of thermoregulation in the febrile response at the central and peripheral levels and cellular events. In response to cold or heat, the brain triggers thermoregulatory responses to coping with changes in body temperature, including autonomic effectors, such as thermogenesis, vasodilation, sweating, and behavioral mechanisms, that trigger flexible, goal-oriented actions, such as seeking heat or cold, nest building, and postural extension. Infrared thermography (IRT) has proven to be a reliable method for the early detection of pathologies affecting animal health and welfare that represent economic losses for farmers. However, the standardization of protocols for IRT use is still needed. Together with the complete understanding of the physiological and behavioral responses involved in the febrile process, it is possible to have timely solutions to serious problem situations. For this reason, the present review aims to analyze the new findings in pathophysiological mechanisms of the febrile process, the heat-loss mechanisms in an animal with fever, thermoregulation, the adverse effects of fever, and recent scientific findings related to different pathologies in farm animals through the use of IRT.

Putative antihyperpyretic factor induced by LPS in spleen of guinea pigs

2005 ◽  
Vol 289 (3) ◽  
pp. R680-R687 ◽  
Author(s):  
Carlos Feleder ◽  
Vit Perlik ◽  
Ying Tang ◽  
Clark M. Blatteis
Keyword(s):  
Kupffer Cells ◽  
Guinea Pigs ◽  
Collateral Circulation ◽  
Splenic Vein ◽  
Inhibitory Factor ◽  
Febrile Response ◽  
Temperature Changes ◽  
The Core ◽  
Temporally Correlated

We reported previously that the onset of LPS-induced fever, irrespective of its route of administration, is temporally correlated with the appearance of LPS in the liver and that splenectomy significantly increases both the febrile response to LPS and the uptake of LPS by Kupffer cells (KC). To further evaluate the role of the spleen in LPS fever production, we ligated the splenic vein and, 7 and 30 days later, monitored the core temperature changes over 6 h after intraperitoneal (ip) injection of LPS (2 μg/kg). Both the febrile response and the uptake of LPS by KC were significantly augmented. Like splenectomy, splenic vein ligation (SVL) increased the febrile response and LPS uptake by KC until the collateral circulation developed, suggesting that the spleen may normally contribute an inhibitory factor that limits KC uptake of LPS and thus affects the febrile response. Subsequently, to verify the presence of this factor, we prepared splenic extracts from guinea pigs pretreated with LPS (8 μg/kg ip) or pyrogen-free saline, homogenized and ultrafiltered them, and injected them intravenously into splenectomized (Splex) guinea pigs pretreated with LPS (8 μg/kg ip). The results confirmed our presumption that the splenic extract from LPS-treated guinea pigs inhibits the exaggerated febrile response and the LPS uptake by the liver of Splex guinea pigs, indicating the presence of a putative splenic inhibitory factor, confirming the participation of the spleen in LPS-induced fever, and suggesting the existence of a novel antihyperpyretic mechanism. Preliminary data indicate that this factor is a lipid.

Intracellular calcium responses in CF/T43 cells: calcium pools and influx pathways

1997 ◽  
Vol 273 (2) ◽  
pp. L363-L373 ◽  
Author(s):  
R. A. Harris ◽  
D. J. Pon ◽  
S. Katz ◽  
J. W. Hanrahan
Keyword(s):  
Threshold Concentration ◽  
Epithelial Cell Line ◽  
Second Phase ◽  
Airway Epithelial ◽  
Histamine Concentration ◽  
Cyclic Monophosphate ◽  
Influx Pathways ◽  
Histamine Response ◽  
Second Peak ◽  
Initial Peak

We studied the intracellular free Ca2+ concentration ([Ca2+]i) response to histamine in a cystic fibrosis airway epithelial cell line (CF/T43). Histamine (100 microM; duration approximately 10 min) biphasically increased [Ca2+]i, with a rapid initial peak (30-45 s) followed by a smaller second peak that lasted for several minutes before returning to baseline. Neither peak specifically depended on Ca2+ influx. Exposure to bradykinin (10 microM) elicited a single peak that lasted 3-3.5 min before returning to baseline. Bradykinin increased intracellular inositol 1,4,5-trisphosphate (IP3), which peaked and returned to baseline within 150 s. Histamine also increased IP3 monophasically, but the peak was brief (< 20 s). Both phases of the Ca2+ response to histamine exhibited similar responsiveness to histamine concentration and sensitivity to antagonists. Cimetidine or thioperamide (1 mM) had no effect on the second peak. Pyrilamine blocked the second peak at concentrations similar to those required to block the initial peak. Activation of the second peak was observed at a threshold concentration of 1 microM comparable with the threshold of the initial peak. Neither adenosine 3',5'-cyclic monophosphate, guanosine 3',5'-cyclic monophosphate, nor cyclic ADP (cADP)-ribose altered the second phase of the histamine response.

Effect of Restraint on Body Temperature in Guinea Pigs

1958 ◽  
Vol 12 (2) ◽  
pp. 214-216 ◽  
Author(s):  
Charles G. Wilber ◽  
Paul F. Robinson
Keyword(s):  
Body Temperature ◽  
Guinea Pigs

scholarly journals Effects of anti-inflammatory drugs on fever and neutrophilia induced byClostridium difficiletoxin B

1996 ◽  
Vol 5 (3) ◽  
pp. 183-187 ◽  
Author(s):  
R. A. Cardoso ◽  
A. A. Melo Filho ◽  
M. C. C. Melo ◽  
D. M. Lyerly ◽  
T. D. Wilkins ◽  
...  
Keyword(s):  
Body Temperature ◽  
Clostridium Difficile ◽  
Intravenous Injection ◽  
Febrile Response ◽  
Toxin B ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Dose Dependent Increase ◽  
Dose Dependent

This study investigated the ability ofClostridium difficiletoxin B, isolated from the VPI 10463 strain, to induce fever and neutrophilia in rats. Intravenous injection of toxin B (0.005–0.5 μg/kg) evoked a dose-dependent increase in body temperature. The febrile response to 0.5 μg/kg of the toxin started in 2.5 h, peaked at 5 h, and subsided fully within 24 h. Toxin B also induced a dosedependent neutrophilia. Pretreatment with indomethacin (2 mg/kg, i.p.) did not affect the neutrophilia induced by toxin B, but significantly reduced the febrile response measured 4 to 8 h after toxin B injection. Dexamethasone (0.5 mg/ kg) also markedly diminished the febrile response induced by toxin B. These results show thatClostridium difficiletoxin B induced a febrile response susceptible to inhibition by dexamethasone and indomethacin. Furthermore, they suggest that prostaglandins are not involved in the neutrophilia caused by this toxin.

scholarly journals Effect of chronic hypercapnia on body temperature regulation

1975 ◽  
Vol 38 (5) ◽  
pp. 900-906 ◽  
Author(s):  
K. E. Schaefer ◽  
A. A. Messier ◽  
C. Morgan ◽  
G. T. Baker
Keyword(s):  
Body Temperature ◽  
Guinea Pigs ◽  
Time Course ◽  
Prolonged Exposure ◽  
Respiratory Acidosis ◽  
Serotonin Content ◽  
Regulatory Processes ◽  
Transient Rise ◽  
Acid Base Status ◽  
Partial Compensation

Guinea pigs and rats exposed to 15% CO2 for 7 days showed a parallel time course of changes in pH, body temperature (TB), and oxygen consumption (VO2). Between 1 and 6 h of exposure the maximal drop in actual pH occurred in guinea pigs simultaneously with the maximal fall in TB and VO2. During the subsequent period pH TB, VO2 rose again. Skin blood content (heat loss) also exhibited a biphasic pH-dependent time course. Animals showing no partial compensation of respiratory acidosis during 3 days exposure also failed in raising their TB back to normal in this time. The behavior of TB was found to be a good indicator of the acid-base status and adaptive potential of the animals to hypercapnia. Similar results were obtained in rats. Thermo-regulatory processes in the hypothalamus were affected during exposure to 15% CO2. Both guinea pigs and rats showed a decrease in norepinephrine content of the hypothalamus during the first part of exposure reaching a maximal fall at the end of 24 h. The serotonin content increased slightly during this period. During prolonged exposure to 3% CO2 for 7 days, TB showed a transient rise, and VO2 was slightly elevated.

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