Endothelin-1 as a central mediator of LPS-induced fever in rats

Fever induced by E. coli lipopolysaccharide (LPS) in rats is substantially reduced by blockade of central endothelin ET B receptors. This study explores the role of endothelin-1 as a central mediator of fever in rats, by investigating the effect of a pyrogenic dose of LPS on the levels of big endoth...

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Veröffentlicht in:Brain research 2005-12, Vol.1066 (1), p.92-100
Hauptverfasser: Fabricio, Aline S.C., Rae, Giles A., D'Orléans-Juste, Pedro, Souza, Glória E.P.
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container_issue 1
container_start_page 92
container_title Brain research
container_volume 1066
creator Fabricio, Aline S.C.
Rae, Giles A.
D'Orléans-Juste, Pedro
Souza, Glória E.P.
description Fever induced by E. coli lipopolysaccharide (LPS) in rats is substantially reduced by blockade of central endothelin ET B receptors. This study explores the role of endothelin-1 as a central mediator of fever in rats, by investigating the effect of a pyrogenic dose of LPS on the levels of big endothelin-1 and endothelin-1 in the cerebrospinal fluid (CSF) and endothelin-1 in the plasma. We further assessed whether the increase in body temperature caused by central injection of endothelin-1 constitutes solely a hyperthermia or a true integrated febrile response. LPS (5 μg kg −1, i.v.) induced fever which peaked at 1.16 ± 0.24 °C within 2 h and remained stable up to 5 h. CSF levels of immunoreactive (ir) big endothelin-1 decreased to undetectable levels at 3 h after LPS, returning only partially at 5 h post-injection. CSF ir-endothelin-1 levels were undetectable in saline-treated animals, but reached 21.9 ± 5.2 fmol ml −1 at 3 h after LPS treatment. Plasma ir-endothelin-1 levels were unchanged after saline or LPS. Central injection of endothelin-1 (1 pmol, i.c.v.) caused long-lasting increases in body temperature (0.81 ± 0.17 °C, 3 h), but simultaneously decreased tail skin temperature (−1.10 ± 0.26 °C), indicating cutaneous vasoconstriction. Moreover, endothelin-1 induced fever (1.0 ± 0.3 °C, 3 h) when injected into the preoptic area of the anterior hypothalamus (100 fmol), but not i.v. (1 or 10 pmol). These data suggest that endothelin-1 is produced in the brain and acts centrally as a mediator of LPS-induced fever.
doi_str_mv 10.1016/j.brainres.2005.10.037
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This study explores the role of endothelin-1 as a central mediator of fever in rats, by investigating the effect of a pyrogenic dose of LPS on the levels of big endothelin-1 and endothelin-1 in the cerebrospinal fluid (CSF) and endothelin-1 in the plasma. We further assessed whether the increase in body temperature caused by central injection of endothelin-1 constitutes solely a hyperthermia or a true integrated febrile response. LPS (5 μg kg −1, i.v.) induced fever which peaked at 1.16 ± 0.24 °C within 2 h and remained stable up to 5 h. CSF levels of immunoreactive (ir) big endothelin-1 decreased to undetectable levels at 3 h after LPS, returning only partially at 5 h post-injection. CSF ir-endothelin-1 levels were undetectable in saline-treated animals, but reached 21.9 ± 5.2 fmol ml −1 at 3 h after LPS treatment. Plasma ir-endothelin-1 levels were unchanged after saline or LPS. Central injection of endothelin-1 (1 pmol, i.c.v.) caused long-lasting increases in body temperature (0.81 ± 0.17 °C, 3 h), but simultaneously decreased tail skin temperature (−1.10 ± 0.26 °C), indicating cutaneous vasoconstriction. Moreover, endothelin-1 induced fever (1.0 ± 0.3 °C, 3 h) when injected into the preoptic area of the anterior hypothalamus (100 fmol), but not i.v. (1 or 10 pmol). 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Psychology</subject><subject>Hypothalamus</subject><subject>Injections, Intravenous</subject><subject>Lipopolysaccharide</subject><subject>Lipopolysaccharides</subject><subject>Male</subject><subject>Microinjections</subject><subject>Oligopeptides - pharmacology</subject><subject>Piperidines - pharmacology</subject><subject>Preoptic area</subject><subject>Preoptic Area - physiology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Skin Temperature - drug effects</subject><subject>Thermoregulation. Hibernation. Estivation. 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This study explores the role of endothelin-1 as a central mediator of fever in rats, by investigating the effect of a pyrogenic dose of LPS on the levels of big endothelin-1 and endothelin-1 in the cerebrospinal fluid (CSF) and endothelin-1 in the plasma. We further assessed whether the increase in body temperature caused by central injection of endothelin-1 constitutes solely a hyperthermia or a true integrated febrile response. LPS (5 μg kg −1, i.v.) induced fever which peaked at 1.16 ± 0.24 °C within 2 h and remained stable up to 5 h. CSF levels of immunoreactive (ir) big endothelin-1 decreased to undetectable levels at 3 h after LPS, returning only partially at 5 h post-injection. CSF ir-endothelin-1 levels were undetectable in saline-treated animals, but reached 21.9 ± 5.2 fmol ml −1 at 3 h after LPS treatment. Plasma ir-endothelin-1 levels were unchanged after saline or LPS. Central injection of endothelin-1 (1 pmol, i.c.v.) caused long-lasting increases in body temperature (0.81 ± 0.17 °C, 3 h), but simultaneously decreased tail skin temperature (−1.10 ± 0.26 °C), indicating cutaneous vasoconstriction. Moreover, endothelin-1 induced fever (1.0 ± 0.3 °C, 3 h) when injected into the preoptic area of the anterior hypothalamus (100 fmol), but not i.v. (1 or 10 pmol). These data suggest that endothelin-1 is produced in the brain and acts centrally as a mediator of LPS-induced fever.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>16360659</pmid><doi>10.1016/j.brainres.2005.10.037</doi><tpages>9</tpages></addata></record>
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subjects Animals
Antihypertensive Agents - pharmacology
Big endothelin-1
Biological and medical sciences
Body Temperature - drug effects
Cerebrospinal fluid
Endothelin-1
Endothelin-1 - cerebrospinal fluid
Endothelin-1 - metabolism
Endothelin-1 - pharmacology
Endothelin-1 - physiology
Escherichia coli
Fever
Fever - chemically induced
Fever - physiopathology
Fundamental and applied biological sciences. Psychology
Hypothalamus
Injections, Intravenous
Lipopolysaccharide
Lipopolysaccharides
Male
Microinjections
Oligopeptides - pharmacology
Piperidines - pharmacology
Preoptic area
Preoptic Area - physiology
Rats
Rats, Wistar
Skin Temperature - drug effects
Thermoregulation. Hibernation. Estivation. Ecophysiology and environmental effects
Vertebrates: anatomy and physiology, studies on body, several organs or systems
title Endothelin-1 as a central mediator of LPS-induced fever in rats
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