Acute-Phase Proteins

Rapid systemic responders to inflammation.

Acute-phase proteins are circulating proteins whose concentrations change during inflammation. Produced mainly by the liver, they connect local tissue signals with systemic defense, transport, coagulation and repair.

Explore acute-phase proteins →

Acute-phase response at a glance

From local infection or injury to a coordinated systemic response.

1. Infection or injury

Microbial or damage signals activate tissue cells.

2. Immune cells release cytokines

IL-6, IL-1 and TNF help communicate inflammatory signals.

3. Liver response

Hepatocytes change the production of circulating proteins.

4. Altered plasma proteins

Positive reactants rise; negative reactants fall.

5. Systemic defense

Host defense and tissue protection are supported.

Where are acute-phase proteins made?

Liver produces many circulating acute-phase proteins

The liver is the major source of many circulating acute-phase proteins. Other tissues can also produce selected proteins locally.

Positive and negative acute-phase proteins

Positive acute-phase proteins

Increase during inflammation.

C-reactive protein (CRP)
Serum amyloid A (SAA)
Fibrinogen and haptoglobin
Hepcidin and α1-antitrypsin
Ceruloplasmin and selected complement proteins

Negative acute-phase proteins

Decrease during inflammation.

Albumin
Transferrin
Transthyretin
Retinol-binding protein

Magnitude and timing vary by protein, cause and individual. “Negative” describes concentration change, not a harmful function.

How the response unfolds

Cytokine signaling in the liver changes protein synthesis.

Cytokines in blood

Inflammatory signals reach the liver.

Receptor signaling

Receptors activate intracellular pathways.

Gene regulation

STAT3 and other pathways alter transcription.

Synthesis and secretion

Hepatocytes release proteins into circulation.

Major acute-phase proteins

Selected proteins contribute to defense and tissue protection through different functions.

C-reactive protein (CRP)

Recognizes selected microbial and damaged-cell structures; can support complement activation.

Serum amyloid A (SAA)

A major acute-phase apolipoprotein. Persistent elevation can contribute to AA amyloidosis.

Fibrinogen

A coagulation substrate that forms fibrin and contributes to erythrocyte sedimentation.

Haptoglobin

Binds free hemoglobin, limiting oxidative damage and helping clearance.

Hepcidin

Regulates iron availability by reducing ferroportin-mediated iron export.

Alpha-1-antitrypsin (A1AT)

Conceptual alpha-1-antitrypsin binding and inhibiting neutrophil elastase

A protease inhibitor that limits tissue injury from enzymes such as neutrophil elastase.

Ceruloplasmin

A copper-containing ferroxidase involved in iron handling and redox biology.

Why acute-phase proteins matter

Microbial recognition

Some proteins identify microbial or damaged-cell patterns.

Complement activation

CRP and other molecules can link recognition to complement.

Tissue protection

Protease inhibitors and transport proteins limit collateral damage.

Coagulation and repair

Fibrin formation supports local hemostasis and repair.

Iron sequestration

Iron handling changes during inflammation.

What clinicians measure

CRP is a commonly measured marker of inflammation. ESR is an indirect measure influenced by fibrinogen and other factors. Neither identifies the cause by itself.

Results are interpreted with symptoms, history, examination and other tests.

When the response becomes persistent

Prolonged inflammation can sustain acute-phase changes. Chronic infection, inflammatory disease and other conditions can contribute. Persistent SAA elevation can lead to AA amyloid deposition in some patients.