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Critical Care
Published in: Critical Care 1/2009

Open Access 01-02-2009 | Research

Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis

Authors: Michael A Flierl, Philip F Stahel, Daniel Rittirsch, Markus Huber-Lang, Andreas D Niederbichler, L Marco Hoesel, Basel M Touban, Steven J Morgan, Wade R Smith, Peter A Ward, Kyros Ipaktchi

Published in: Critical Care | Issue 1/2009

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Abstract

Introduction

Septic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction during experimental sepsis.

Methods

Using the standardised caecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with either neutralising anti-C5a antibody or pre-immune immunoglobulin (Ig) G as a placebo. Sham-operated animals served as internal controls.

Results

Placebo-treated septic rats showed severe BBB dysfunction within 24 hours, accompanied by a significant upregulation of pituitary C5a receptor and pro-inflammatory cytokine expression, although gene levels of growth hormone were significantly attenuated. The pathophysiological changes in placebo-treated septic rats were restored by administration of neutralising anti-C5a antibody to the normal levels of BBB and pituitary function seen in the sham-operated group.

Conclusions

Collectively, the neutralisation of C5a greatly ameliorated pathophysiological changes associated with septic encephalopathy, implying a further rationale for the concept of pharmacological C5a inhibition in sepsis.
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Metadata
Title
Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis
Authors
Michael A Flierl
Philip F Stahel
Daniel Rittirsch
Markus Huber-Lang
Andreas D Niederbichler
L Marco Hoesel
Basel M Touban
Steven J Morgan
Wade R Smith
Peter A Ward
Kyros Ipaktchi
Publication date
01-02-2009
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2009
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc7710

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