Thursday, 26 February 2009

What is C-reactive protein?

When infection strikes, the body panics and throws a large number of quick-acting but non-specific measures out in the hope that some of them will hit the mark.  Later, more targeted measures are undertaken in addition, once the particular pathogen has been identified.  Broadly, this is the rationale behind the innate and specific immune systems, respectively.

One of the most important components of the non-specific response is the group called the acute phase proteins.  These are proteins whose concentration changes in response to inflammatory cytokines secreted largely by cells of the immune system.  The synthesis of such proteins by the liver may either increase or decrease when the whole apparatus is set into motion.  Although the acute phrase response was probably designed to deal with infections, the cytokine network for any cause of inflammation has sufficient overlap to elicit fundamentally the same response.  Therefore, the acute phase response is best thought of as an indication of inflammation, rather than just infection.

C-reactive protein (CRP) is one such acute phase protein, whose concentration rises rapidly (to abnormally high levels within 6 hours).  Only significant synthetic liver dysfunction has the ability to generate false negatives in this regard, so the CRP test is very "stable" across a wide variety of pathologies. CRP seems to have 3 main categories of action:
  • Anti-infective: CRP can activate complement, and also opsonise particles.  It also helps neutrophils move out from the blood stream to the tissues at sites of inflammation.
  • Anti-inflammatory: CRP helps to damp down the inflammatory response at other sites, however, by preventing white cell adhesion at places showing no signs of inflammation, and by promoting the secretion of anti-inflammatory cytokines.
  • Scavenging: CRP can bind to cells dying from apoptosis or necrosis and thereby activate complement, which aids in the removal of such cells.
The normal range for CRP is usually given as from 0 to 10 mg/L, which is the 99th centile for healthy people.  Some labs prefer to make the cut off lower (e.g. at 5), but this obviously has the disadvantage of labelling more normal people as "sick" (i.e. more false positives).

The serum concentration of CRP declines quickly once the original stimulus (e.g. a bacterial invasion) has been removed - it usually returns to baseline after about 3-7 days.  Furthermore a failure for the CRP to decline significantly within a few days indicates with a reasonably high level of certainty that whatever treatment is being tried isn't working.

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