| The acute phase response is a term which encompasses all of the systemic changes which occur in response to infection or inflammation.
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| As part of this reaction, the liver synthesizes a number of 'acute phase proteins', which have been defined as those hepatically-derived proteins whose plasma concentrations change by more than 25% within 1 week of the inception of the inflammatory or infective insult. The production of these proteins is stimulated by pro-inflammatory cytokines released by macrophages, and of these interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) have a central role in the induction of the acute phase response. The acute phase proteins have a number of different functions in the response to inflammation. Binding proteins, opsonins, such as C-reactive protein (CRP), bind to macromolecules
released by damaged tissue or infective agents and promote their phagocytosis. Complement factors promote the phagocytosis of foreign molecules. Protease inhibitors, such as α1-antitrypsin and α1-antichymotrypsin inhibit proteolytic enzymes. These latter two acute phase proteins also promote fibroblast growth and the production of connective tissue required for the repair and resolution of the injury.
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A substantial supply of amino acids is required as substrates for this increase in hepatic protein synthesis and these are derived from the proteolysis of skeletal muscle.
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| TNF and IL-1 again are involved by stimulating the breakdown of specific intracellular proteins by the ubiquitin-proteosome mechanism (see below).
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| The magnitude of the acute phase protein response often shows a quantitative relationship to the severity of the inflammatory/infective process, such that serial measurements of the serum acute phase proteins by clinical laboratories give useful information about the progress of the disease and its response to treatment. Changes in the serum concentration of CRP are quantitatively the most marked of all the acute phase proteins. Concentrations may increase by one or two orders of magnitude, the response is rapid and CRP has a short half-life. These properties and the relative ease with which it can be measured, have lead to CRP being widely used in clinical practice as a laboratory marker of infection/inflammation (see also Chapter 36).
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