Acute‐Phase Proteins

Abstract

Acute‐phase proteins (APPs) form part of the systemic acute‐phase response which accompanies inflammation. Their primary site of synthesis is the hepatocyte in response to interleukin‐6 and other inflammation‐associated cytokines. Clinically, APPs such as C‐reactive protein provide a useful indicator of the extent of inflammation responding most intensely in severe cases such as sepsis, but showing some response in even mild inflammatory insults or stress. Functions of APPs are still poorly defined but are largely homeostatic and diverse including innate protective immune roles, transport functions, protease inhibition, clotting and metabolic functions. Hepatocytes upregulate secretory pathway networks to allow an increased synthetic activity, although some proteins are actively downregulated. Evidence has mounted to show the importance of APPs for protection of the host.

Key Concepts

  • Acute‐phase proteins are increased in response to inflammatory stimuli within 12–72 h.
  • Functions include direct innate recognition, innate immune response in control of inflammation and immunity, transport of a variety of metabolic and micronutrient factors, enzymes and proteins involved in clotting and thrombosis and so on.
  • Hepatocytes are the main source of acute‐phase proteins.
  • Induction is mainly through transcriptional control through STAT3 and other factors.
  • Concentrations return to normal when inflammation subsides and thus they provide a useful rapidly responding clinical marker of inflammation.
  • Some proteins have increased synthesis to replace that consumed (e.g. complement or clotting components) others are required to fulfil new requirements (e.g. lipocalin‐2).
  • The acute‐phase proteins should be viewed as an important part of the overall systemic response to inflammation (acute‐phase response).

Keywords: acute‐phase proteins; acute‐phase response; inflammation; cytokines; C‐reactive protein; serum amyloid A

Figure 1. A typical acute‐phase response showing the induction and return to normal levels over time following a typical short inflammatory stimulus such as surgery trauma. Serum amyloid A (SAA) and C‐reactive protein (CRP) show a rapid response while serpin A1 (ACT) and α1‐acid glycoprotein (AGP) show a slower response.
Figure 2. The acute‐phase protein response is regulated both directly and indirectly by a complex network of intercellular signalling molecules involving cytokines, cytokine modulators and other hormones. Inflammation‐associated cytokines, produced by cells at the inflammatory site and probably by distant cells as well, induce changes in production of acute‐phase proteins by hepatocytes.
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Further Reading

Baumann H and Gauldie J (1994) The acute‐phase response. Immunology Today 15: 74–80.

Gabay C and Kushner I (1999) Acute‐phase proteins and other systemic responses to inflammation. New England Journal of Medicine 340 (6): 448–454.

Raynes JG (2010) Acute phase response Topley and Wilson's Microbiology and Microbial Infections. Immunology, Chapter 12, pp. 193–214.

Volanakis JE (1997) Acute phase proteins in rheumatic disease. In: Koopman WJ (ed) Arthritis and Allied Conditions: A Textbook of Rheumatology, pp. 505–514. Baltimore: Williams & Wilkins.

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Raynes, John G(Sep 2015) Acute‐Phase Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000497.pub2]