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Vol. 12, No. 2, 2005
Issue release date: March 2005
Section title: Original Paper
Neuroimmunomodulation 2005;12:67–80
(DOI:10.1159/000083578)

Complement Component C5a Is Integral to the Febrile Response of Mice to Lipopolysaccharide

Li S. · Boackle S.A. · Holers V.M. · Lambris J.D. · Blatteis C.M.
Departments of aPhysiology, University of Tennessee Health Science Center, Memphis, Tenn., bMedicine, University of Colorado Health Science Center, Denver, Colo., and cPathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pa., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 1/28/2004
Accepted: 3/23/2004
Published online: 3/17/2005

Number of Print Pages: 14
Number of Figures: 9
Number of Tables: 0

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: http://www.karger.com/NIM

Abstract

Objectives: The complement system is critical to the febrile response of mice to intraperitoneally administered lipopolysaccharide (LPS). We previously identified C3 and C5 as two components potentially involved in this response. This study was designed to examine whether the complement system is also pivotal in the response of mice to intravenously or intracerebroventricularly injected LPS, to distinguish between C3 and C5 and their cognate derivatives as the essential mediator(s), and to determine whether the failure of complement-deficient mice to develop a fever could be due to their possible inability to secrete pyrogenic cytokines. Methods: Wild-type (WT; C57BL/6J) mice, hypocomplemented or not by intravenously injected cobra venom factor (10 U/mouse), and C3-, CR3- and C5-sufficient and -deficient mice were intravenously challenged with LPS (0.25 µg/mouse); WT and C3–/– mice pretreated with a C5a receptor antagonist (C5aRa) were similarly challenged. In addition, the serum levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 were compared in LPS-treated C5+/+ and C5–/– mice. Results: LPS induced a 1°C rise in core temperature in all the mice, except C5–/– mice and those pretreated with C5aRa. C5+/+ and C5–/– mice challenged intracerebroventricularly with LPS exhibited identical febrile responses. LPS induced similar increases in the serum levels of IL-1β, TNFα and IL-6 in C5+/+ and C5–/– mice. Conclusions: C5a is crucial for the development of febrile responses to LPS in mice; its site of action is peripheral, not central. The possibility that an inability to produce cytokines could account for the failure of C5–/– mice to develop a fever is not supported.


  

Author Contacts

Shuxin Li, MD, PhD
Department of Physiology, The University of Tennessee Health Science Center
894 Union Avenue
Memphis, TN 38163 (USA)
Tel. +1 901 448 5748, Fax +1 901 448 1673, E-Mail lshuxin@physio1.utmem.edu

  

Article Information

Received: January 28, 2004
Accepted: March 23, 2004
Number of Print Pages : 14
Number of Figures : 9, Number of Tables : 0, Number of References : 87

  

Publication Details

Neuroimmunomodulation

Vol. 12, No. 2, Year 2005 (Cover Date: Released March 2005)

Journal Editor: G.P. Chrousos, Bethesda, Md.
ISSN: 1021–7401 (print), 1423–0216 (Online)

For additional information: http://www.karger.ch/nim


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 1/28/2004
Accepted: 3/23/2004
Published online: 3/17/2005

Number of Print Pages: 14
Number of Figures: 9
Number of Tables: 0

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: http://www.karger.com/NIM


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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