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

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


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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism*
  • Complement C5a / antagonists & inhibitors*
  • Complement C5a / immunology*
  • Immunoglobulin G / pharmacology
  • Immunoglobulin G / therapeutic use
  • Male
  • Pituitary Diseases / metabolism*
  • Pituitary Diseases / physiopathology
  • Pituitary Diseases / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Anaphylatoxin C5a / antagonists & inhibitors
  • Receptor, Anaphylatoxin C5a / biosynthesis
  • Sepsis / complications
  • Sepsis / drug therapy
  • Sepsis / metabolism*


  • Immunoglobulin G
  • Receptor, Anaphylatoxin C5a
  • Complement C5a