Acute-phase response and fever (CRP, ESR, procalcitonin) !

Process

During inflammation the liver makes alarm proteins and the brain raises body temperature; blood tests can measure these changes.

Updated 2026-11-01

See it in 3D: Liver

What it is

Cytokines released by activated macrophages, mainly IL-1, IL-6 and TNF, act at a distance: the liver changes the proteins it secretes (acute-phase response) and the hypothalamus raises the temperature set point (fever). Acute-phase proteins such as CRP and fibrinogen are the basis of common inflammation tests. Procalcitonin rises mainly in serious bacterial infection.

Function

Fever speeds leukocyte activity and slows the growth of many pathogens.
Hepcidin lowers serum iron, withholding iron from microbes; chronically, this causes anemia of inflammation.
CRP binds microbial surfaces and acts as an opsonin and complement activator.

Step by step

Microbes or tissue damage activate macrophages through pattern recognition receptors.
Macrophages release IL-1, IL-6 and TNF (endogenous pyrogens) into the blood.
In the hypothalamus these cytokines induce cyclooxygenase-2 and prostaglandin E2.
PGE2 raises the thermoregulatory set point: vasoconstriction and shivering produce heat until body temperature reaches it.
In the liver, IL-6 increases CRP, fibrinogen, serum amyloid A, ferritin and hepcidin, and lowers albumin and transferrin.
When the stimulus ends, the set point falls back and the body loses heat by vasodilation and sweating.

Common markers of inflammation

Marker	What it reflects	Key point
CRP	Liver protein induced by IL-6	Rises within hours and falls quickly; useful to follow; does not locate the cause
ESR	Speed at which red cells settle, increased mainly by fibrinogen	Rises and falls slowly; also affected by anemia, age and immunoglobulins
Procalcitonin	Released by many tissues in systemic bacterial infection	Helps separate bacterial from viral illness; high values suggest sepsis
Ferritin	Iron storage protein and acute-phase reactant	May be high in inflammation even when iron stores are low
Albumin	Negative acute-phase protein	Falls during sustained inflammation

Clinical notes

Anemia of chronic disease (inflammation): low serum iron, high ferritin, driven by hepcidin.
Antipyretics such as NSAIDs and acetylsalicylic acid lower fever by blocking cyclooxygenase and PGE2 synthesis.
Persistently high ESR suggests diseases such as giant cell arteritis, multiple myeloma or chronic infection, but it is not specific.

Test yourself

Think of the answer, then tap the question to see it.

Which mediator acts directly on the hypothalamus to raise the temperature set point?

Prostaglandin E2, produced by cyclooxygenase-2 after stimulation by IL-1, IL-6 and TNF.

Which cytokine is the main stimulus for hepatic CRP synthesis?

IL-6.

Why does ESR rise during inflammation?

Fibrinogen and other plasma proteins rise and make red cells stack together (rouleaux), so they settle faster.

What is the main clinical use of procalcitonin?

It helps tell a serious bacterial infection or sepsis from viral illness and can be followed during treatment.

Why do patients with chronic inflammation develop anemia with high ferritin?

IL-6 increases hepcidin, which traps iron inside macrophages and blocks intestinal absorption; ferritin rises as an acute-phase protein.

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See it in 3D

The structures of Durgical's 3D anatomy where it is found.

Liver

In Pharmacology

← All of immunology

Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.

Sources: C-Reactive Protein (CRP) Test (MedlinePlus, U.S. National Library of Medicine, 2024); Procalcitonin Test (MedlinePlus, U.S. National Library of Medicine, 2024); 17.5 Inflammation and Fever (OpenStax (Microbiology), 2016).

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Representative model, for educational purposes only.