Acute-phase Proteins

The discovery of large amounts of C-reactive protein (CRP) in the serum of patients during the acute phase of pneumococcal pneumonia in 1930 focused interest on the plasma protein changes that accompany inflammatory states. CRP and other plasma proteins whose concentrations rose significantly under such circumstances were accordingly referred to as acute-phase proteins (APP). The subsequent realization that concentrations of some other plasma proteins decrease led to their designation as negative APPs, while the earlier recognizedAPPs are often referred to as positive APPs. It is now appreciated that APP changes are only part of a large number of systemic manifestations, distant from inflammatory sites, that replace normal homeostasis during inflammatory states (Figure 1). APP changes are not limited to acute illness, but persist during a great variety of chronic inflammatory states as well, constituting a semantically paradoxical chronic acute-phase response. A change of approximately 25% in plasma concentrationhas been suggested as thedefinitionof anAPP (Morley and Kushner, 1982). Changes in plasma protein concentrations largely result from alterations in synthesis by hepatocytes in response to circulating inflammationassociated cytokines. While other cells, including macrophages, fibroblasts, epithelial cells and adipocytes can also produce APPs, it is unlikely that synthesis at these sites contributes significantly to plasma concentrations. In humans, many different stimuli can induce the acutephase response, including bacterial (and to a lesser extent viral) infection, trauma, surgical procedures, burn injury, tissue infarction, various immunologically and crystalmediated inflammatory disorders, advancedmalignancies, strenuous exercises, childbirth and heatstroke.