Systemic but not central administration of tumor necrosis factor-α attenuates LPS-induced fever in rats

J. J. Klir, J. L. McClellan, W. Kozak, Z. Szelényi, G. H W Wong, M. J. Kluger

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The purpose of this study was to test the hypothesis that tumor necrosis factor-α (TNF) limits fever induced by lipopolysaccharide (LPS) in rats and to determine whether such antipyretic action of this cytokine is outside or inside the central nervous system (CNS). The CNS effects on LPS-induced fever were tested by injecting a subpyrogenic amount (0.20 μg) of human recombinant TNF (hrTNF) intracerebroventricularly or by slowly infusing into the anterior hypothalamus an amount previously measured in this brain region during LPS fever (0.24 U in 0.13 μl of artificial cerebrospinal fluid/min). The peripheral effects of this cytokine on LPS fever were tested by injecting 1 μg/kg of hrTNF intraperitoneally or by intraperitoneal administration of 300 μg/kg of the hrTNF soluble receptor p80 (hrTNFsr). The core temperature (measured by biotelemetry) during LPS fever was not significantly affected by administration of hrTNF intracerebroventricularly or intrahypothalamically. An intraperitoneal injection of hrTNF (1 μg/kg) had a significant antipyretic effect on febrile response to LPS (mean temperature 2-8 h after injections was 37.28 ± 0.12°C in rats injected with hrTNF and LPS vs. 38.73 ± 0.04°C in rats injected with saline and LPS; analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P <0.05). When rats were injected intraperitoneally with hrTNFsr, the febrile response to LPS was enhanced (analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P <0.05). These results support the hypothesis that TNF acts to limit the magnitude of LPS-induced fever and that this action occurs outside the CNS.

Original languageEnglish
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume268
Issue number2 37-2
Publication statusPublished - 1995

Fingerprint

Lipopolysaccharides
Fever
Tumor Necrosis Factor-alpha
Antipyretics
Central Nervous System
Analysis of Variance
Cytokines
Anterior Hypothalamus
Temperature
Tumor Necrosis Factor Receptors
Intraperitoneal Injections
Cerebrospinal Fluid
Injections
Brain

ASJC Scopus subject areas

  • Physiology

Cite this

Systemic but not central administration of tumor necrosis factor-α attenuates LPS-induced fever in rats. / Klir, J. J.; McClellan, J. L.; Kozak, W.; Szelényi, Z.; Wong, G. H W; Kluger, M. J.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 268, No. 2 37-2, 1995.

Research output: Contribution to journalArticle

@article{e39aee8ea22b4c8c97f2ab308684ce3d,
title = "Systemic but not central administration of tumor necrosis factor-α attenuates LPS-induced fever in rats",
abstract = "The purpose of this study was to test the hypothesis that tumor necrosis factor-α (TNF) limits fever induced by lipopolysaccharide (LPS) in rats and to determine whether such antipyretic action of this cytokine is outside or inside the central nervous system (CNS). The CNS effects on LPS-induced fever were tested by injecting a subpyrogenic amount (0.20 μg) of human recombinant TNF (hrTNF) intracerebroventricularly or by slowly infusing into the anterior hypothalamus an amount previously measured in this brain region during LPS fever (0.24 U in 0.13 μl of artificial cerebrospinal fluid/min). The peripheral effects of this cytokine on LPS fever were tested by injecting 1 μg/kg of hrTNF intraperitoneally or by intraperitoneal administration of 300 μg/kg of the hrTNF soluble receptor p80 (hrTNFsr). The core temperature (measured by biotelemetry) during LPS fever was not significantly affected by administration of hrTNF intracerebroventricularly or intrahypothalamically. An intraperitoneal injection of hrTNF (1 μg/kg) had a significant antipyretic effect on febrile response to LPS (mean temperature 2-8 h after injections was 37.28 ± 0.12°C in rats injected with hrTNF and LPS vs. 38.73 ± 0.04°C in rats injected with saline and LPS; analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P <0.05). When rats were injected intraperitoneally with hrTNFsr, the febrile response to LPS was enhanced (analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P <0.05). These results support the hypothesis that TNF acts to limit the magnitude of LPS-induced fever and that this action occurs outside the CNS.",
author = "Klir, {J. J.} and McClellan, {J. L.} and W. Kozak and Z. Szel{\'e}nyi and Wong, {G. H W} and Kluger, {M. J.}",
year = "1995",
language = "English",
volume = "268",
journal = "American Journal of Physiology",
issn = "0363-6119",
publisher = "American Physiological Society",
number = "2 37-2",

}

TY - JOUR

T1 - Systemic but not central administration of tumor necrosis factor-α attenuates LPS-induced fever in rats

AU - Klir, J. J.

AU - McClellan, J. L.

AU - Kozak, W.

AU - Szelényi, Z.

AU - Wong, G. H W

AU - Kluger, M. J.

PY - 1995

Y1 - 1995

N2 - The purpose of this study was to test the hypothesis that tumor necrosis factor-α (TNF) limits fever induced by lipopolysaccharide (LPS) in rats and to determine whether such antipyretic action of this cytokine is outside or inside the central nervous system (CNS). The CNS effects on LPS-induced fever were tested by injecting a subpyrogenic amount (0.20 μg) of human recombinant TNF (hrTNF) intracerebroventricularly or by slowly infusing into the anterior hypothalamus an amount previously measured in this brain region during LPS fever (0.24 U in 0.13 μl of artificial cerebrospinal fluid/min). The peripheral effects of this cytokine on LPS fever were tested by injecting 1 μg/kg of hrTNF intraperitoneally or by intraperitoneal administration of 300 μg/kg of the hrTNF soluble receptor p80 (hrTNFsr). The core temperature (measured by biotelemetry) during LPS fever was not significantly affected by administration of hrTNF intracerebroventricularly or intrahypothalamically. An intraperitoneal injection of hrTNF (1 μg/kg) had a significant antipyretic effect on febrile response to LPS (mean temperature 2-8 h after injections was 37.28 ± 0.12°C in rats injected with hrTNF and LPS vs. 38.73 ± 0.04°C in rats injected with saline and LPS; analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P <0.05). When rats were injected intraperitoneally with hrTNFsr, the febrile response to LPS was enhanced (analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P <0.05). These results support the hypothesis that TNF acts to limit the magnitude of LPS-induced fever and that this action occurs outside the CNS.

AB - The purpose of this study was to test the hypothesis that tumor necrosis factor-α (TNF) limits fever induced by lipopolysaccharide (LPS) in rats and to determine whether such antipyretic action of this cytokine is outside or inside the central nervous system (CNS). The CNS effects on LPS-induced fever were tested by injecting a subpyrogenic amount (0.20 μg) of human recombinant TNF (hrTNF) intracerebroventricularly or by slowly infusing into the anterior hypothalamus an amount previously measured in this brain region during LPS fever (0.24 U in 0.13 μl of artificial cerebrospinal fluid/min). The peripheral effects of this cytokine on LPS fever were tested by injecting 1 μg/kg of hrTNF intraperitoneally or by intraperitoneal administration of 300 μg/kg of the hrTNF soluble receptor p80 (hrTNFsr). The core temperature (measured by biotelemetry) during LPS fever was not significantly affected by administration of hrTNF intracerebroventricularly or intrahypothalamically. An intraperitoneal injection of hrTNF (1 μg/kg) had a significant antipyretic effect on febrile response to LPS (mean temperature 2-8 h after injections was 37.28 ± 0.12°C in rats injected with hrTNF and LPS vs. 38.73 ± 0.04°C in rats injected with saline and LPS; analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P <0.05). When rats were injected intraperitoneally with hrTNFsr, the febrile response to LPS was enhanced (analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P <0.05). These results support the hypothesis that TNF acts to limit the magnitude of LPS-induced fever and that this action occurs outside the CNS.

UR - http://www.scopus.com/inward/record.url?scp=0028950377&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028950377&partnerID=8YFLogxK

M3 - Article

C2 - 7864244

AN - SCOPUS:0028950377

VL - 268

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 2 37-2

ER -