Acute-phase proteins (APPs) are a class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the acute-phase reaction (also called acute-phase response). The terms acute-phase protein and acute-phase reactant (APR) are often used synonymously, although some APRs are (strictly speaking) polypeptides rather than proteins.
In response to injury, local inflammatory cells (neutrophil granulocytes and macrophages) secrete a number of cytokines into the bloodstream, most notable of which are the interleukins IL1, IL6 and IL8, and TNF?. The liver responds by producing a large number of acute-phase reactants. At the same time, the production of a number of other proteins is reduced; these proteins are, therefore, referred to as "negative" acute-phase reactants. Increased acute-phase proteins from the liver may also contribute to the promotion of sepsis.
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Positive
Positive acute-phase proteins serve (part of the innate immune system) different physiological functions for the immune system. Some act to destroy or inhibit growth of microbes, e.g., C-reactive protein, mannose-binding protein, complement factors, ferritin, ceruloplasmin, serum amyloid A and haptoglobin. Others give negative feedback on the inflammatory response, e.g. serpins. Alpha 2-macroglobulin and coagulation factors affect coagulation, mainly stimulating it. This pro-coagulant effect may limit infection by trapping pathogens in local blood clots. Also, some products of the coagulation system can contribute to the innate immune system by their ability to increase vascular permeability and act as chemotactic agents for phagocytic cells.
Negative
"Negative" acute-phase proteins decrease in inflammation. Examples include albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, transcortin. The decrease of such proteins may be used as markers of inflammation. The physiological role of decreased synthesis of such proteins is generally to save amino acids for producing "positive" acute-phase proteins more efficiently. Theoretically, a decrease in transferrin could additionally be decreased by an upregulation of transferrin receptors, but the latter does not appear to change with inflammation.
Clinical significance
Measurement of acute-phase proteins, especially C-reactive protein, is a useful marker of inflammation in both medical and veterinary clinical pathology. It correlates with the erythrocyte sedimentation rate (ESR), however not always directly. This is due to the ESR being largely dependent on elevation of fibrinogen, an acute phase reactant with a half-life of approximately one week. This protein will therefore remain higher for longer despite removal of the inflammatory stimuli. In contrast, C-reactive protein (with a half-life of 6-8 hours) rises rapidly and can quickly return to within the normal range if treatment is employed. For example, in active systemic lupus erythematosus, one may find a raised ESR but normal C-reactive protein.
They may also indicate liver failure.
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