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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.


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


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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