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.

Microinjection of a cyclooxygenase inhibitor into the anteroventral preoptic region attenuates LPS fever

1998 ◽  
Vol 274 (3) ◽  
pp. R783-R789 ◽  
Author(s):  
Thomas E. Scammell ◽  
John D. Griffin ◽  
Joel K. Elmquist ◽  
Clifford B. Saper
Keyword(s):  
Cerebrospinal Fluid ◽  
Body Temperature ◽  
Preoptic Area ◽  
Prostaglandin Synthesis ◽  
Cyclooxygenase Inhibitor ◽  
Preoptic Region ◽  
Considerable Evidence ◽  
Artificial Cerebrospinal Fluid ◽  
Intravenous Ketorolac

Considerable evidence supports the role of prostaglandins in fever production, but the neuroanatomic sites of prostaglandin synthesis that produce fever remain unknown. With the use of a novel microinjection technique, we injected the cyclooxygenase inhibitor ketorolac into the preoptic area (POA) to determine which preoptic regions produce the prostaglandins required for fever. Initial experiments demonstrated that intravenous ketorolac blocked the fever normally produced by lipopolysaccharide (LPS) 5 μg/kg iv. Microinjection of ketorolac into the POA had no effect on body temperature, and injection of artificial cerebrospinal fluid into the POA did not alter LPS fever. Injection of ketorolac into the anteroventral POA markedly decreased the fever produced by LPS, compared with injections into more rostral, caudal, or dorsal locations. These observations indicate that prostaglandin synthesis in the anteroventral preoptic region is necessary for the production of fever.

Elevated CSF osmolality inhibits thermoregulatory heat loss responses

1986 ◽  
Vol 251 (4) ◽  
pp. R749-R754 ◽  
Author(s):  
E. Turlejska ◽  
M. A. Baker
Keyword(s):  
Cerebrospinal Fluid ◽  
Body Temperature ◽  
Ambient Temperature ◽  
Heat Loss ◽  
Preoptic Area ◽  
Brain Temperature ◽  
High Ambient Temperature ◽  
Evaporative Heat Loss ◽  
Artificial Cerebrospinal Fluid ◽  
Hot Environments

The effect of intracerebroventricular (icv) infusions of hypertonic NaCl or sucrose on thermoregulatory responses to heat was studied in conscious rabbits to test the idea that brain osmoreceptors are involved in the inhibition of evaporative heat loss and elevation of body temperature in dehydrated mammals at high ambient temperature (Ta). In rabbits hydrated ad lib and resting at a Ta of 33 degrees C, icv infusion (3.4 microliter/min) of hypertonic (1,500 mosm) NaCl or sucrose in artificial cerebrospinal fluid (ACSF) produced a significant reduction in respiratory frequency (f) and in ear skin temperature (Te) and a rise in brain temperature (preoptic area, Tpoa). icv infusion of ACSF alone or ACSF + NaCl at 500 and at 750 mosm had no effect on f or on Te or Tpoa. Infusion of NaCl + ACSF at 1,000 mosm reduced f but did not affect Te or Tpoa. In hydrated rabbits, icv infusion of 1,500 mosm NaCl abolished the rise in f and in Te elicited by POA heating at Ta of 25 degrees C. In dehydrated rabbits at 33 degrees C, f was below hydrated levels and icv infusion of water (6.8 microliter/min) produced a reversible elevation in f. These findings suggest that brain osmoreceptors can influence thermoregulation in hot environments.

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.

Body temperature response to IL-1 beta in pregnant rats

1995 ◽  
Vol 269 (5) ◽  
pp. R1179-R1182 ◽  
Author(s):  
R. L. Simrose ◽  
J. E. Fewell
Keyword(s):  
Body Temperature ◽  
Intravenous Injection ◽  
Interleukin 1 ◽  
Temperature Response ◽  
Sprague Dawley ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Pregnant Rats ◽  
Sprague Dawley Rats ◽  
Near Term

Rats have an attenuated or absent febrile response to exogenous pyrogen (e.g., bacterial endotoxin) near term of pregnancy. With the aim of providing insight into possible mechanism(s) of the altered febrile response to exogenous pyrogen, experiments have been carried out on 67 time-bred Sprague-Dawley rats to investigate the febrile response to endogenous pyrogen [i.e., interleukin-1 beta (IL-1 beta)]. On day 13 of gestation, intravenous injection of IL-1 beta produced a significant increase in body temperature with a latency of approximately 30 min and a duration of approximately 120 min. In contrast, on days 17 and 21 of gestation as well as on the day of delivery, intravenous injection of IL-1 beta produced significant decreases in body temperature. Thus rats do not develop fever in response to endogenous pyrogen near term of pregnancy but rather become hypothermic. The mechanism of the altered body temperature response to exogenous pyrogen as pregnancy proceeds remains unknown. We speculate, however, that it most likely lies downstream from the formation of endogenous pyrogen.

Peptide neurohormones: their role in thermoregulation and fever

1983 ◽  
Vol 61 (7) ◽  
pp. 579-593 ◽  
Author(s):  
W. D. Ruwe ◽  
W. L. Veale ◽  
K. E. Cooper
Keyword(s):  
Body Temperature ◽  
Anterior Commissure ◽  
Extracellular Fluid ◽  
Current Evidence ◽  
Central Administration ◽  
Febrile Response ◽  
Axonal Projections ◽  
The Central Nervous System ◽  
Convulsive Disorders ◽  
The Brain

The neural elements of the rostral diencephalon in the mammal have been implicated in the regulation of body temperature. Moreover, it may be the neural elements within this region of the brain which activate the febrile mechanisms in response to pyrogen. Is it possible that the neuropeptides located within this area of the brain serve as neurochemical intermediaries involved in temperature regulation, fever, and (or) antipyresis? Central administration of several neuropeptides can elicit marked changes in the core temperature of an animal. Although most of these purative neuroregulators exert only a very minor influence on thermoregulation, a small number of the neuropeptides have been shown to have a profound effect on the system controlling this basic vegetative function. One of these peptides, arginine vasopressin (AVP) may play a role as an endogenous antipyretic. The neuroanatomical localization of this peptide, as well as its axonal projections, are consistent with such a role for this neurohypophyseal peptide in the mediation of antipyresis. In addition, current evidence suggests that AVP does function as a neurotransmitter. Examination of the febrile response to pyrogen in both the periparturient animal and the neonate indicates that an elevation in plasma levels of AVP is closely correlated with the diminution in the febrile response. Also, when AVP is perfused into punctate regions of the brain, a pyrogen-induced fever may be markedly suppressed. AVP appears to act primarily within the septal area, 2- to 3-mm rostral to the anterior commissure. During the development of fever, the release of AVP is altered within these same loci. As body temperature decreases during the febrile state, there is a concomitant increase in the amount of AVP released into the extracellular fluid of these septal sites. Very recent findings suggest that AVP may have additional central neurochemical functions. For example, this peptide may be involved in the etiology of some forms of convulsive disorders. The precise manner in which body temperature is regulated by the central nervous system normally and during fever is not well understood. In particular, the central mechanism of action of AVP in these processes remains to be determined. Currently, it is clear that the critical central mechanisms which are active in thermoregulation and fever are quite complex and will require many more years of investigation before the exact role of each can be enunciated.

Dehydration enhances endotoxin fever by increased production of endogenous pyrogen

1986 ◽  
Vol 251 (1) ◽  
pp. R41-R47 ◽  
Author(s):  
A. Morimoto ◽  
N. Murakami ◽  
T. Ono ◽  
T. Watanabe
Keyword(s):  
Immune Response ◽  
Body Temperature ◽  
Prostaglandin E2 ◽  
Intravenous Injection ◽  
Blood Parameters ◽  
Significant Rise ◽  
The Body ◽  
Hypotonic Solution ◽  
Endogenous Pyrogen

The febrile responses in rats to an intravenous injection of the bacterial endotoxin Salmonella typhosa were investigated under normally hydrated and dehydrated conditions. When endotoxin was injected intravenously into the dehydrated rats, a biphasic-patterned fever resulted, whereas in normal rats an intravenous injection of endotoxin did not induce fever. No significant differences in febrile responses to the intravenous endogenous pyrogen (EP), prostaglandin E2, and intracerebroventricular prostaglandin E2 between normal and dehydrated rats were observed. When the blood plasma obtained from rats with endotoxin-induced fever under dehydrated conditions was transferred to the normal rats, a significant rise in the body temperature was induced. The effect of hydration by an administration of the hypotonic solution after dehydration was examined in endotoxin-induced fever and in changes of the basic blood parameters. It is concluded that febrile responses to endotoxin during dehydrated condition are caused by an increased production of EP. The migration of leukocytes from circulation to any other tissue will be an important factor in producing EP under dehydrated conditions. Furthermore, under dehydrated condition, EP may be produced by numerous macrophages in tissues in vivo, where many kinds of leukocytes migrate and exchange signals with each other in developing an immune response.

Febrile nonresponsiveness of vagotomized animals: is it due to endotoxin translocation from the gut and tolerance?

1998 ◽  
Vol 275 (3) ◽  
pp. R933-R935 ◽  
Author(s):  
Andrej A. Romanovsky
Keyword(s):  
Cerebrospinal Fluid ◽  
Preoptic Area ◽  
Prostaglandin Synthesis ◽  
Cyclooxygenase Inhibitor ◽  
Preoptic Region ◽  
Considerable Evidence ◽  
Artificial Cerebrospinal Fluid ◽  
Endotoxin Translocation ◽  
Intravenous Ketorolac

The following is the abstract of the article discussed in the subsequent letter: Scammell, Thomas E., John D. Griffin, Joel K. Elmquist, and Clifford B. Saper. Microinjection of a cyclooxygenase inhibitor into the anteroventral preoptic region attenuates LPS fever. Am. J. Physiol.274 ( Regulatory Integrative Comp. Physiol. 43): R933–R935, 1998.—Considerable evidence supports the role of prostaglandins in fever production, but the neuroanatomic sites of prostaglandin synthesis that produce fever remain unknown. With the use of a novel microinjection technique, we injected the cyclooxygenase inhibitor ketorolac into the preoptic area (POA) to determine which preoptic regions produce the prostaglandins required for fever. Initial experiments demonstrated that intravenous ketorolac blocked the fever normally produced by lipopolysaccharide (LPS) 5 μg/kg iv. Microinjection of ketorolac into the POA had no effect on body temperature, and injection of artificial cerebrospinal fluid into the POA did not alter LPS fever. Injection of ketorolac into the anteroventral POA markedly decreased the fever produced by LPS, compared with injections into more rostral, caudal, or dorsal locations. These observations indicate that prostaglandin synthesis in the anteroventral preoptic region is necessary for the production of fever.

scholarly journals Lipopolysaccharide-Induced Fever Depends on Prostaglandin E2 Production Specifically in Brain Endothelial Cells

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4849-4861 ◽  
Author(s):  
Linda Engström ◽  
Johan Ruud ◽  
Anna Eskilsson ◽  
Anders Larsson ◽  
Ludmila Mackerlova ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cerebrospinal Fluid ◽  
Prostaglandin E2 ◽  
Hematopoietic Cells ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Brain Endothelial Cells ◽  
Febrile Response ◽  
Pge2 Synthesis ◽  
The Brain

Abstract Immune-induced prostaglandin E2 (PGE2) synthesis is critical for fever and other centrally elicited disease symptoms. The production of PGE2 depends on cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (mPGES-1), but the identity of the cells involved has been a matter of controversy. We generated mice expressing mPGES-1 either in cells of hematopoietic or nonhematopoietic origin. Mice lacking mPGES-1 in hematopoietic cells displayed an intact febrile response to lipopolysaccharide, associated with elevated levels of PGE2 in the cerebrospinal fluid. In contrast, mice that expressed mPGES-1 only in hematopoietic cells, although displaying elevated PGE2 levels in plasma but not in the cerebrospinal fluid, showed no febrile response to lipopolysaccharide, thus pointing to the critical role of brain-derived PGE2 for fever. Immunohistochemical stainings showed that induced cyclooxygenase-2 expression in the brain exclusively occurred in endothelial cells, and quantitative PCR analysis on brain cells isolated by flow cytometry demonstrated that mPGES-1 is induced in endothelial cells and not in vascular wall macrophages. Similar analysis on liver cells showed induced expression in macrophages and not in endothelial cells, pointing at the distinct role for brain endothelial cells in PGE2 synthesis. These results identify the brain endothelial cells as the PGE2-producing cells critical for immune-induced fever.

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.

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