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Acute-phase protein

Acute-phase proteins 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).

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 TNFα. 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 are, therefore, referred to as "negative" acute-phase reactants. Increased acute phase proteins from the liver may also contribute to the promotion of sepsis.[1]


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,[2] 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.[citation needed] 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.

"Positive" acute-phase proteins:
Protein Immune system function
C-reactive protein Opsonin on microbes[3] (not an acute-phase reactant in mice)
Serum amyloid P component Opsonin
Serum amyloid A
Complement factors Opsonization, lysis and clumping of target cells. Chemotaxis
Mannan-binding lectin Mannan-binding lectin pathway of complement activation
Fibrinogen, prothrombin, factor VIII,
von Willebrand factor
Coagulation factors, trapping invading microbes in blood clots.
Some cause chemotaxis
Plasminogen Degradation of blood clots
Alpha 2-macroglobulin
Ferritin Binding iron, inhibiting microbe iron uptake [5]
Hepcidin[6] Stimulates the internalization of ferroportin, preventing release of iron bound by ferritin within intestinal enterocytes and macrophages
Ceruloplasmin Oxidizes iron, facilitating for ferritin, inhibiting microbe iron uptake
Haptoglobin Binds hemoglobin, inhibiting microbe iron uptake
(Alpha-1-acid glycoprotein, AGP)
Steroid carrier
Alpha 1-antitrypsin Serpin, downregulates inflammation
Alpha 1-antichymotrypsin Serpin, downregulates inflammation


"Negative" acute-phase proteins decrease in inflammation. Examples include albumin,[7] transferrin,[7] transthyretin,[7] 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.[8]

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.[9]

See also


  1. ^ Abbas, A., Lichtman, A., & Pillai, S. (2012). Basic immunology Functions and Disorders of the Immune System (4th ed., p. 40). Philadelphia, PA: Saunders/Elsevier.
  2. ^ B L Herpers, H Endeman, B A W de Jong, B M de Jongh, J C Grutters, D H Biesma, and H van Velzen-Blad. Acute-phase responsiveness of mannose-binding lectin in community-acquired pneumonia is highly dependent upon MBL2 genotypes. Clin Exp Immunol. 2009 Jun;156(3):488-94. PMID 19438602
  3. ^ Lippincott's Illustrated Reviews: Immunology. Paperback: 384 pages. Publisher: Lippincott Williams & Wilkins; (July 1, 2007). Language: English. ISBN 0-7817-9543-5. ISBN 978-0-7817-9543-2. Page 182
  4. ^ Boer JP, Creasey AA, Chang A, Abbink JJ et al. (1993). "Alpha-2-macroglobulin functions as an inhibitor of fibrinolytic, clotting, and neutrophilic proteinases in sepsis: studies using a baboon model". Infect Immun 61 (12): 5035–5043. 
  5. ^
  6. ^ Vecchi C, Montosi G, Zhang K et al. (August 2009). "ER stress controls iron metabolism through induction of hepcidin". Science 325 (5942): 877–80. PMC 2923557. PMID 19679815. doi:10.1126/science.1176639. 
  7. ^ a b c Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O, Ledue TB, Craig WY (1999). "Reference distributions for the negative acute-phase serum proteins, albumin, transferrin, and transthyretin: a practical, simple and clinically relevant approach in a large cohort". J. Clin. Lab. Anal. 13 (6): 273–9. PMID 10633294. doi:10.1002/(SICI)1098-2825(1999)13:6<273::AID-JCLA4>3.0.CO;2-X. 
  8. ^ Chua E, Clague JE, Sharma AK, Horan MA, Lombard M (October 1999). "Serum transferrin receptor assay in iron deficiency anaemia and anaemia of chronic disease in the elderly". QJM 92 (10): 587–94. PMID 10627880. doi:10.1093/qjmed/92.10.587. 
  9. ^ Ananian P, Hardwigsen J, Bernard D, Le Treut YP (2005). "Serum acute-phase protein level as indicator for liver failure after liver resection". Hepatogastroenterology 52 (63): 857–61. PMID 15966220. 

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