Increase in concentration of acute phase reactants (APR) comprises a major pathophysiologic phenomenon that accompanies inflammation and tissue injury [1,2]. With the acute phase response, normal homeostatic mechanisms are replaced by new set points that presumably contribute to defensive or adaptive capabilities.
Focus on the acute phase phenomenon first occurred with the discovery of C-reactive protein (CRP) in the serum of patients during the acute phase of pneumococcal pneumonia [3,4]. CRP consists of five identical, non-covalently associated subunits, each with a molecular weight of approximately 23 kD, which are arranged symmetrically around a central pore . CRP and related proteins with this structure are termed pentraxins; others include serum amyloid P and a number of pattern recognition molecules referred to as long pentraxins . (See "An overview of the innate immune system", section on 'Pentraxins'.)
Despite its name, APR accompany both acute and chronic inflammatory states. They can occur in association with a wide variety of disorders, including infection, trauma, infarction, inflammatory arthritides, and various neoplasms.
Acute phase proteins are defined as those proteins whose serum concentrations increase or decrease by at least 25 percent during inflammatory states . Such proteins are termed either positive or negative APR, respectively. Changes in the levels of APR largely reflect altered production by hepatocytes.
Increases in APR can vary from approximately 50 percent for ceruloplasmin and several components of the complement cascade to 1000-fold or more for CRP and serum amyloid A. Other positive APR include fibrinogen, alpha-1 antitrypsin, haptoglobin, interleukin (IL)-1 receptor antagonist, hepcidin, ferritin, procalcitonin, and others [7-9]. Procalcitonin is of particular interest; while it behaves as a rapidly responding acute phase protein, it has relatively high specificity for infection [10-12]. In contrast to other recognized APR, which are synthesized by hepatocytes, its site of origin is uncertain. (See 'Infection' below.)