Acute-phase proteins ( APPs) are a class of whose concentrations in blood plasma either 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 acute-phase reaction characteristically involves fever, acceleration of peripheral leukocytes, circulating and their precursors.
In response to injury, local inflammation cells (neutrophil granulocytes and ) secrete a number of into the bloodstream, most notable of which are the IL1, and IL6, and TNF-α. The liver responds by producing many acute-phase reactants. At the same time, the production of a number of other is reduced; these are, therefore, referred to as "negative" acute-phase reactants. Increased acute-phase proteins from the liver may also contribute to the promotion of sepsis.
Regulation of synthesis
TNF-α, IL-1β and
Interferon gamma are important for the expression of inflammatory mediators such as
and
, and they also cause the production of platelet-activating factor and IL-6. After stimulation with proinflammatory
,
produce IL-6 in the liver and present it to the
. IL-6 is the major mediator for the hepatocytic secretion of APPs. Synthesis of APP can also be regulated indirectly by
cortisol. Cortisol can enhance expression of IL-6 receptors in liver cells and induce IL-6-mediated production of APPs.
Positive
Positive acute-phase proteins serve (as part of the innate immune system) different physiological functions within the
immune system. Some act to destroy or inhibit growth of
Microorganism, 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.
. Alpha 2-macroglobulin and coagulation factors affect
coagulation, mainly stimulating it. This pro-coagulant effect may limit
infection by trapping
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
.
| + "Positive" acute-phase proteins:
! Protein !! Immune system function |
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Negative
"Negative" acute-phase proteins decrease in inflammation. Examples include
albumin,
,
[ 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 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.]
While the production of C3 (a complement factor) increases in the liver, the plasma concentration often lowers because of an increased turn-over, therefore it is often seen as a negative acute-phase protein.
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 the elevation of fibrinogen, an acute phase reactant with a half-life of approximately one week. This protein will therefore remain higher for longer despite the 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.
External links
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http://eclinpath.com/chemistry/proteins/acute-phase-proteins/
