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).