Acute-phase proteins are a class of protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

. This response is called the acute-phase reaction (also called acute-phase response).
In response to injury, local inflammatory

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 cells (neutrophil granulocyte

Neutrophil granulocyte

Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...

s and macrophage

Macrophage

Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s) secrete a number of cytokine

Cytokine

Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

s into the bloodstream, most notable of which are the interleukin

Interleukin

Interleukins are a group of cytokines that were first seen to be expressed by white blood cells . The term interleukin derives from "as a means of communication", and "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes"...

s IL-1, IL-6

Interleukin 6

Interleukin-6 is a protein that in humans is encoded by the IL6 gene.IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other...

 and IL-8

Interleukin 8

Interleukin-8 is a chemokine produced by macrophages and other cell types such as epithelial cells. It is also synthesized by endothelial cells, which store IL-8 in their storage vesicles, the Weibel-Palade bodies...

, and TNF-α.

The liver

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 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 are, therefore, referred to as "negative" acute-phase reactants. As such, increased acute phase proteins from the liver may also contribute to the promotion of sepsis

Sepsis

Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...

.

Positive

Positive acute-phase proteins serve different physiological functions for the immune system

Immune system

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

. Some act to destroy or inhibit growth of microbes, e.g., C-reactive protein

C-reactive protein

C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...

, Mannose-binding protein, complement factors, ferritin

Ferritin

Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...

, ceruloplasmin

Ceruloplasmin

Ceruloplasmin is a ferroxidase enzyme that in humans is encoded by the CP gene.Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948...

, Serum amyloid A

Serum amyloid A

Serum amyloid A proteins are a family of apolipoproteins associated with high-density lipoprotein in plasma. Different isoforms of SAA are expressed constitutively at different levels or in response to inflammatory stimuli . These proteins are produced predominantly by the liver...

 and haptoglobin

Haptoglobin

Haptoglobin is a protein that in humans is encoded by the HP gene. In blood plasma, haptoglobin binds free hemoglobin released from erythrocytes with high affinity and thereby inhibits its oxidative activity. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system...

. Others give negative feedback

Negative feedback

Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...

 on the inflammatory response, e.g. serpin

Serpin

Serpins are a group of proteins with similar structures that were first identified as a set of proteins able to inhibit proteases. The acronym serpin was originally coined because many serpins inhibit chymotrypsin-like serine proteases .The first members of the serpin superfamily to be extensively...

s. Alpha 2-macroglobulin

Alpha 2-macroglobulin

alpha-2-Macroglobulin, also known as α2-macroglobulin and abbreviated as α2M and A2M, is a large plasma protein found in the blood. It is produced by the liver, and is a major component of the alpha-2 band in protein electrophoresis....

 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

Innate immune system

The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...

 by their ability to increase vascular permeability and act as chemotactic agents for phagocytic cells.

"Positive" acute-phase proteins:

Protein	Immune system Immune system An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...  function
C-reactive protein C-reactive protein C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...	Opsonin Opsonin An opsonin is any molecule that targets an antigen for an immune response. However, the term is usually used in reference to molecules that act as a binding enhancer for the process of phagocytosis, especially antibodies, which coat the negatively-charged molecules on the membrane. Molecules that...  on microbes
Serum amyloid P component Serum Amyloid P component Amyloid P component, serum is the identical serum form of amyloid P component , a 25kDa pentameric protein first identified as the pentagonal constituent of in vivo pathological deposits called "amyloid"...	Opsonin
Serum amyloid A Serum amyloid A Serum amyloid A proteins are a family of apolipoproteins associated with high-density lipoprotein in plasma. Different isoforms of SAA are expressed constitutively at different levels or in response to inflammatory stimuli . These proteins are produced predominantly by the liver...	Recruitment of immune cells to inflammatory sites Inhibition of enzyme Enzyme Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates... s that degrade extracellular matrix Extracellular matrix In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
Complement Complement system The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...  factors	Opsonization, lysis Lysis Lysis refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate"....  and clumping of target cells. Chemotaxis Chemotaxis Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
Mannan-binding lectin Mannan-binding lectin Mannose-binding lectin , also named mannose- or mannan-binding protein , is an important factor in innate immunity.-Function:MBL belongs to the class of collectins in the C-type lectin superfamily, whose function appears to be pattern recognition in the first line of defense in the pre-immune...	Mannan-binding lectin pathway Mannan-binding lectin pathway The Mannan-binding lectin pathway is similar in structure to the classical complement pathway, in that, after activation, it proceeds through the action of C4 and C2 to produce activated complement proteins further down the cascade...  of complement activation
Fibrinogen Fibrinogen Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for... , prothrombin, factor VIII Factor VIII Factor VIII is an essential blood clotting factor also known as anti-hemophilic factor . In humans, Factor VIII is encoded by the F8 gene... , von Willebrand factor Von Willebrand factor von Willebrand factor is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome...	Coagulation factors, trapping invading microbes in blood clots. Some cause chemotaxis
Plasminogen	Degradation of blood clots
Alpha 2-macroglobulin	Inhibitor of coagulation Coagulation Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...  by inhibiting thrombin Thrombin Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss... . Inhibitor of fibrinolysis Fibrinolysis Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...  by inhibiting plasmin Plasmin Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notably, fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.- Function :...
Ferritin Ferritin Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...	Binding iron, inhibiting microbe iron uptake
Hepcidin Hepcidin Hepcidin is a peptide hormone produced by the liver. It was discovered in 2000, and appears to be the master regulator of iron homeostasis in humans and other mammals. In humans, HAMP is the gene that encodes for hepcidin.-Structure:...	Stimulates the internalization of ferroportin Ferroportin Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of it. It is found on the surface of cells that store or transport iron, including:*Enterocytes in the duodenum*Hepatocytes... , preventing release of iron Iron Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...  bound by ferritin Ferritin Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...  within intestinal enterocytes and macrophages
Ceruloplasmin Ceruloplasmin Ceruloplasmin is a ferroxidase enzyme that in humans is encoded by the CP gene.Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948...	Oxidizes iron, facilitating for ferritin, inhibiting microbe iron uptake
Haptoglobin Haptoglobin Haptoglobin is a protein that in humans is encoded by the HP gene. In blood plasma, haptoglobin binds free hemoglobin released from erythrocytes with high affinity and thereby inhibits its oxidative activity. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system...	Binds hemoglobin Hemoglobin Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates... , inhibiting microbe iron uptake
Orosomucoid (Alpha-1-acid glycoprotein, AGP) Orosomucoid Orosomucoid or alpha-1-acid glycoprotein is an acute phase plasma alpha-globulin glycoprotein and is modulated by two polymorphic genes. It is synthesized primarily in hepatocytes and has a normal plasma concentration between 0.6-1.2 mg/mL...	Steroid carrier
Alpha 1-antitrypsin Alpha 1-antitrypsin Alpha 1-Antitrypsin or α1-antitrypsin is a protease inhibitor belonging to the serpin superfamily. It is generally known as serum trypsin inhibitor. Alpha 1-antitrypsin is also referred to as alpha-1 proteinase inhibitor because it inhibits a wide variety of proteases...	Serpin, downregulates inflammation
Alpha 1-antichymotrypsin Alpha 1-antichymotrypsin Alpha 1-antichymotrypsin is an alpha globulin glycoprotein that is a member of the serpin superfamily.It inhibits the activity of certain enzymes called proteases, such as cathepsin G that is found in neutrophils, and chymases found in mast cells, by cleaving them into a different shape or...	Serpin, downregulates inflammation

Negative

"Negative" acute-phase proteins decrease in inflammation. Examples include albumin

Albumin

Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...

, transferrin

Transferrin

Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...

, transthyretin

Transthyretin

Transthyretin is a serum and cerebrospinal fluid carrier of the thyroid hormone thyroxine and retinol binding protein bound to retinol. This is how transthyretin gained its name, transports thyroxine and retinol...

, retinol-binding protein, antithrombin

Antithrombin

Antithrombin is a small protein molecule that inactivates several enzymes of the coagulation system. Antithrombin is a glycoprotein produced by the liver and consists of 432 amino acids. It contains three disulfide bonds and a total of four possible glycosylation sites...

, transcortin

Transcortin

Transcortin, also corticosteroid-binding globulin or CBG, is officially called serpin peptidase inhibitor, clade A , member 6.It is an alpha-globulin.-Binding:...

. 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 acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s for producing "positive" acute-phase proteins more efficiently. Theoretically, a decrease in transferrin could additionally be decreased by an upregulation of transferrin receptor

Transferrin receptor

Transferrin receptor is a carrier protein for transferrin. It is needed for the import of iron into the cell and is regulated in response to intracellular iron concentration...

s, 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

Clinical pathology

Clinical pathology , Laboratory Medicine , Clinical analysis or Clinical/Medical Biology , is a medical specialty that is concerned with the diagnosis of disease based on the laboratory analysis of bodily fluids, such as...

. It correlates with the erythrocyte sedimentation rate

Erythrocyte sedimentation rate

The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...

(ESR).

They may also indicate liver failure