Acute phase proteins
On this page
Definition:
Acute phase proteins (APPs), sometimes referred to acute phase reactants, are plasma proteins whose concentrations change by ≥25% during inflammation, infection, trauma, or tissue injury.Production and regulation:
Acute phase proteins (APPs) are primarily synthesised in the liver by hepatocytes. The acute phase response is mainly driven by pro-inflammatory cytokines released from macrophages, dendritic cells, and other immune cells in response to infection or tissue damage.Key regulators:
- IL-6: primary inducer of most positive APPs (CRP, fibrinogen, hepcidin, serum amyloid A).
- IL-1β & TNF-α: synergise with IL-6 to promote fever and neutrophil mobilisation.
- IL-10 & glucocorticoids: modulate the response (can enhance some APPs but generally dampen excessive inflammation).
Cytokines are key regulators. They bind to hepatocyte surface receptors and influence gene expression (primarily via activation of the JAK/STAT3 pathway). This up-regulates transcription of genes encoding positive APPs and down-regulates negative APPs (albumin, transferrin).
Note APPs may be classed as positive or negative:
- Positive APPs increase to promote host defence and limit microbial growth.
- Negative APPs decrease to conserve amino acids and energy for the increased synthesis of positive APPs.
| Positive APPs (increase in inflammation) | Negative APPs (decrease in inflammation) |
|---|---|
| All downregulated to conserve amino acids for synthesis of positive APPs |