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PMID: 8551238 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interleukin (IL)-6 gene expression in the central nervous system is necessary for fever response to lipopolysaccharide or IL-1 beta: a study on IL-6-deficient mice.

The Journal of experimental medicine ·Vol. 183 ·No. 1 ·1996-01-01 ·Pages 311-6

Chai Z, Gatti S, Toniatti C, Poli V, Bartfai T

Abstract

Interleukin (IL)-6, IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) are considered to act as endogenous pyrogens. Because of the complex pattern of cross-inductions between these cytokines, the relative role of the central and peripheral production of these cytokines in eliciting the fever response has not yet been clarified. The purpose of this study was to determine the role of IL-6 in the fever response by making use of mice carrying a null mutation in the IL-6 gene. The intraperitoneal injections of lipopolysaccharide (LPS) (50 micrograms/kg) and recombinant murine (rm) IL-1 beta (10 micrograms/kg), respectively, failed to evoke fever response in IL-6-deficient mice, whereas the same doses of LPS and rmIL-1 beta caused fever response in wild-type mice. The fever response could be induced in the IL-6-deficient mice by intracerebroventricular injection of recombinant human (rh) IL-6 (500 ng/mouse), whereas intracerebroventricular injection of rmIL-1 beta (100 ng/mouse) failed to produce fever response in the IL-6-deficient mice. These results suggest that central IL-6 is a necessary component of the fever response to both endogenous (IL-1 beta) and exogenous (LPS) pyrogens in mice and that IL-6 acts downstream from both peripheral and central IL-1 beta.

MeSH Terms
Animals Body Temperature Brain/metabolism Fever/etiology Interleukin-1/pharmacology Interleukin-6/deficiency,genetics,metabolism Lipopolysaccharides/pharmacology Male Mice Mice, Mutant Strains Pyrogens/pharmacology Recombinant Proteins/metabolism
Chemicals
Interleukin-1 Interleukin-6 Lipopolysaccharides Pyrogens Recombinant Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chai Z
Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Gatti S
Toniatti C
Poli V
Bartfai T
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.183.1.311
Published
1996-01-01
Pages
311-6
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192408
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.183.1.311 PMC Full Text View journal details
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