Acute-phase proteins (acute-phase reactants) include the soluble proteins found in the blood whose levels in the serum increase (positive APP) or decrease (negative APP) in case of inflammation and tissue injury.
There is a bunch of proteins/polypeptides which concentration in blood changes significantly (at least by more than 25% and even up to 100-fold) due to inflammatory processes and tissue damage as a result of the so-called acute phase response – a non-specific body’s reaction. Acute phase reactants are widely used in clinical settings to test the degree of inflammation. These substances are synthesized mainly in the liver and enter the bloodstream in response to metabolic changes triggered by inflammation, stress, infection, traumatic injuries, and malignancies. APPs synthesis is regulated by inflammatory cytokines including interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor (TNF).
Positive acute-phase proteins
Concentration of these proteins in the serum usually rises within 1-2 days following the initiation of the inflammatory process. If there are no further stimuli the APR levels return to their normal values in 4-7 days, however, in chronic inflammation there is constant proinflammatory cytokines production and, respectively, APR levels remain high. The degree of increase defines the category of APP as a major, moderate or minor.
Major proteins increase 10- to 1000-fold (С-reactive protein, serum amyloid A), moderate – 2- to 10-fold (fibrinogen and haptoglobin), whereas minor proteins increase only slightly (ceruloplasmin) in response to inflammation. Furthermore, minor and moderate APP remains increased for a long time that is characteristic of chronic inflammatory processes.
- Cross-reactive protein (CRP) was one of the first proteins recognized as an acute phase reactant. In case of acute inflammation (namely, infection) CRP levels rise up to 50000-fold. This fact may be explained by its significant role in infection clearance and innate immunity.
Elevated CRP levels are also associated with increased risk of diabetes mellitus, cardiovascular disorders, and cerebrovascular diseases.
- Serum amyloid A (SAA) is produced in inflammation by the liver and recruits the immune cells to the sites of infection.
- Haptoglobin is synthesized not only in the liver but also in kidneys, lungs and even skin. This protein binds free hemoglobin, so its levels decrease in hemolytic anemia. As a result, iron-utilizing bacteria cannot engulf hemoglobin.
- Fibrinogen levels (normal concentration of 200-400 mg/dL) rise in the presence of inflammation as this substance takes part in acute phase response and is responsible for wound healing and coagulation.
- Alpha-1 acid glycoprotein (orosomucoid) is widely used as a predictor for a 5-year risk of all-cause mortality.
- Ceruloplasmin is well-known as copper transporting protein, it also eliminates the superoxides produced by the neutrophils. It is produced by activated macrophages. Furthermore, this protein is also used to predict cardiovascular risks.
- Alpha-1 antitrypsin inhibits the protease trypsin and modifies the immune system function by affecting the immune cells.
- The mannose-binding protein binds a wide range of bacteria and other microorganisms that represent mannose and some other sugars (polysaccharides) on their surfaces. By thus the pathogens are marked as non-self (in the process known as opsonization) and destruction of the invading organisms occurs.
Negative acute-phase proteins
Acute-phase reactants which levels decrease in response to inflammation
As long as it involves the proteins in the inflammatory process therefore albumin levels drop significantly.
- Transferrin plays a role in innate immunity. It is suggested that decreased levels of transferrin create a bactericidal environment in which bacteria die.
- Transthyretin (prealbumin) binds thyroid hormones and retinol and enhances lymphocytes maturation. Its synthesis decreases in inflammation and tissue injury.
Acute-phase proteins are used to determine the grade of inflammation and/or tissue injury and to evaluate treatment response and its efficacy. Some of the acute phase proteins such as C-reactive protein, serum amyloid A (SAA), fibrinogen, ferritin, and ceruloplasmin appear elevated in cardiovascular diseases and may be used to predict potential mortality and morbidity.