[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Immunology](https://durgical.com/en/immunology/) › [Innate immunity](https://durgical.com/en/immunology/#a-innate) › Acute-phase response and fever (CRP, ESR, procalcitonin)

[Immunology](https://durgical.com/en/immunology/) · [Innate immunity](https://durgical.com/en/immunology/#a-innate)

# 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](https://durgical.com/en/anatomy/liver/)

## Key points

- IL-1, IL-6 and TNF are the endogenous pyrogens; PGE2 in the hypothalamus raises the set point.
- IL-6 is the main driver of hepatic CRP production.
- CRP changes fast; ESR changes slowly and depends largely on fibrinogen.
- Procalcitonin rises mainly in systemic bacterial infection.
- Hepcidin from the liver lowers serum iron: anemia of inflammation.

## 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.

## Memory aid

Three cytokines, two targets: IL-1, IL-6 and TNF turn up the brain's thermostat and change the liver's shopping list.

## 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.

[Add to my cards (5)](https://durgical.app/estudiar/?add=/en/immunology/acute-phase-response-and-fever/)

## See it in 3D

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

- [Liver](https://durgical.com/en/anatomy/liver/)

## Related

- [Acute inflammation: vascular and cellular events](https://durgical.com/en/immunology/acute-inflammation-vascular-and-cellular-events/)
- [Pattern recognition: PAMPs, DAMPs, Toll-like receptors](https://durgical.com/en/immunology/pattern-recognition-pamps-damps-toll-like-receptors/)
- [Innate immunity (overview, barriers)](https://durgical.com/en/immunology/innate-immunity/)
- [Interleukin-1](https://durgical.com/en/immunology/interleukin-1/)
- [Interleukin-6](https://durgical.com/en/immunology/interleukin-6/)
- [TNF-α](https://durgical.com/en/immunology/tnf/)
- [Cytokines: the table to know](https://durgical.com/en/immunology/cytokines-the-table-to-know/)

## Related conditions

- [Sepsis and septic shock](https://durgical.com/en/conditions/sepsis-and-septic-shock/)
- [Community-acquired pneumonia](https://durgical.com/en/conditions/community-acquired-pneumonia/)

## In Pharmacology

- [Nonsteroidal anti-inflammatory drugs (NSAIDs)](https://durgical.com/en/pharmacology/classes/nonsteroidal-anti-inflammatory-drugs/)
- [Acetylsalicylic acid](https://durgical.com/en/pharmacology/acetylsalicylic-acid/)

[← All of immunology](https://durgical.com/en/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](https://medlineplus.gov/lab-tests/c-reactive-protein-crp-test/) (MedlinePlus, U.S. National Library of Medicine, 2024); [Procalcitonin Test](https://medlineplus.gov/lab-tests/procalcitonin-test/) (MedlinePlus, U.S. National Library of Medicine, 2024); [17.5 Inflammation and Fever](https://openstax.org/books/microbiology/pages/17-5-inflammation-and-fever) (OpenStax (Microbiology), 2016).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/immunology/acute-phase-response-and-fever/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/immunology/acute-phase-response-and-fever/