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Crit Care. 2009;13(1):R12. doi: 10.1186/cc7710. Epub 2009 Feb 6.

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

Author information

1
Department of Orthopaedic Surgery, Denver Health Medical Center, University of Colorado School of Medicine, Denver, CO 80204, USA. michael.flierl@dhha.org

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.

PMID:
19196477
PMCID:
PMC2688129
DOI:
10.1186/cc7710
[Indexed for MEDLINE]
Free PMC Article

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