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[General pathology](https://durgical.com/en/general-pathology/) · [Inflammation](https://durgical.com/en/general-pathology/#a-inflammation)

# Systemic effects of inflammation: fever, acute-phase proteins, leukocytosis, sepsis

- Mechanism

Strong inflammation spills into the blood: cytokines cause fever, make the liver release acute-phase proteins and the marrow release white cells.

Updated 2026-11-01

## Key points

- Endogenous pyrogens: IL-1, TNF, IL-6 → hypothalamic COX-2 → PGE2 → higher set point.
- IL-6 → liver acute-phase proteins: CRP, fibrinogen, serum amyloid A, hepcidin and ferritin up; albumin and transferrin down.
- High fibrinogen → rouleaux → high ESR.
- Hepcidin → anaemia of chronic disease; years of high serum amyloid A → AA amyloidosis.
- Sepsis = life-threatening organ dysfunction caused by a dysregulated host response to infection.

## What it is

The acute-phase response is the body-wide reaction to cytokines released by inflammation, mainly IL-1, TNF and IL-6. It produces fever, a change in the proteins made by the liver, leukocytosis, a fast heart rate, sleepiness and loss of appetite. It is the basis of everyday tests (CRP, ESR, white cell count) and, when cytokines flood the circulation, of sepsis and septic shock.

## Step by step

- Microbial products (exogenous pyrogens such as LPS) stimulate macrophages to release IL-1, TNF and IL-6 (endogenous pyrogens).
- In the hypothalamus these cytokines induce COX-2, and prostaglandin E2 raises the thermoregulatory set point.
- The body conserves and makes heat (skin vasoconstriction, shivering) until it reaches the new set point: chills come first.
- IL-6 makes hepatocytes produce acute-phase proteins (CRP, fibrinogen, serum amyloid A, hepcidin) and less albumin.
- IL-1 and TNF release neutrophils from the marrow reserve; colony-stimulating factors raise production: leukocytosis with left shift.
- Hepcidin traps iron in macrophages and blocks its absorption in the gut: anaemia of chronic disease.
- With massive cytokine release (sepsis): vasodilation, capillary leak, DIC, insulin resistance and organ failure.

## White cell changes and what they suggest

| Finding | Typical causes |
| --- | --- |
| Neutrophilia with left shift (band forms) | Bacterial infection, tissue necrosis |
| Lymphocytosis | Viral infections (infectious mononucleosis, hepatitis), pertussis |
| Eosinophilia | Helminths, allergy, some drug reactions |
| Leukopenia | Typhoid fever, some viral and rickettsial infections, overwhelming sepsis, alcohol use |
| Leukemoid reaction | Very high count that resembles leukaemia, from severe infection or inflammation |

## Clinical notes

- Antipyretics such as NSAIDs and paracetamol lower fever by reducing PGE2 synthesis in the hypothalamus.
- In Colombia, a multicentre study in tertiary emergency departments of Medellín examined how the site of infection relates to in-hospital death in sepsis.

## In the lab

- CRP rises within hours and falls quickly when inflammation settles, so it is useful to follow an infection.
- ESR: fibrinogen and immunoglobulins reduce the repulsion between red cells, which stack (rouleaux) and settle faster; it changes more slowly than CRP.
- Procalcitonin rises more in bacterial than in viral infection and helps guide antibiotic decisions in some settings.
- Ferritin is an acute-phase reactant: a normal or high value does not exclude iron deficiency during inflammation.

## Memory aid

When the liver hears IL-6 it sounds the alarm (CRP), mixes the glue (fibrinogen), padlocks the iron (hepcidin) and turns down albumin.

## Test yourself

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

## How do cytokines raise body temperature?

IL-1, TNF and IL-6 induce COX-2 in the hypothalamus; the prostaglandin E2 produced raises the set point, so the body conserves and makes heat.

## Why does the ESR rise in inflammation?

Acute-phase fibrinogen neutralises the negative surface charge of red cells, so they stack in rouleaux and sediment faster.

## Which acute-phase protein causes anaemia of chronic disease, and how?

Hepcidin: it degrades ferroportin, trapping iron in macrophages and enterocytes so less reaches the bone marrow.

## Which acute-phase protein forms the deposits of secondary (AA) amyloidosis?

Serum amyloid A, produced for years in chronic inflammation such as rheumatoid arthritis or familial Mediterranean fever.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/systemic-effects-of-inflammation-fever-acute-phase-proteins-leukocytosis-sepsis/)

## Related

- [Mediators of inflammation: the table to know](https://durgical.com/en/general-pathology/mediators-of-inflammation-the-table-to-know/)
- [How septic shock develops](https://durgical.com/en/general-pathology/how-septic-shock-develops/)
- [Shock: types, stages and the organs it damages](https://durgical.com/en/general-pathology/shock-types-stages-and-the-organs-it-damages/)
- [Disseminated intravascular coagulation: how consumption causes both clots and bleeding](https://durgical.com/en/general-pathology/disseminated-intravascular-coagulation-how-consumption-causes-both-clots-and-ble/)
- [Chronic inflammation: causes, cells and features](https://durgical.com/en/general-pathology/chronic-inflammation-causes-cells-and-features/)
- [Inflammation: the cardinal signs and its five steps](https://durgical.com/en/general-pathology/inflammation-the-cardinal-signs-and-its-five-steps/)

## Related conditions

- [Sepsis and septic shock](https://durgical.com/en/conditions/sepsis-and-septic-shock/)
- [Neonatal sepsis](https://durgical.com/en/conditions/neonatal-sepsis/)
- [Anaemia of chronic disease (anaemia of inflammation)](https://durgical.com/en/conditions/anaemia-of-chronic-disease/)
- [Amyloidosis](https://durgical.com/en/conditions/amyloidosis/)
- [Familial Mediterranean fever and other hereditary autoinflammatory syndromes](https://durgical.com/en/conditions/familial-mediterranean-fever-and-other-hereditary-autoinflammatory-syndromes/)
- [Rheumatoid arthritis](https://durgical.com/en/conditions/rheumatoid-arthritis/)
- [Toxic shock syndrome](https://durgical.com/en/conditions/toxic-shock-syndrome/)
- [Typhoid (enteric) fever](https://durgical.com/en/conditions/typhoid-fever/)
- [Community-acquired pneumonia](https://durgical.com/en/conditions/community-acquired-pneumonia/)

## Elsewhere in DurgiPedia

- [Acute-phase response and fever (CRP, ESR, procalcitonin)](https://durgical.com/en/immunology/acute-phase-response-and-fever/)
- [Fever](https://durgical.com/en/physiology/fever/)
- [Body temperature regulation](https://durgical.com/en/physiology/body-temperature-regulation/)
- [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/)
- [Plasma proteins and electrophoresis](https://durgical.com/en/biochemistry/topics/plasma-proteins-and-electrophoresis/)

## In Pharmacology

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

[← All of general pathology](https://durgical.com/en/general-pathology/)

Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [C-Reactive Protein (CRP) Test: MedlinePlus Medical Test](https://medlineplus.gov/lab-tests/c-reactive-protein-crp-test/) (MedlinePlus, US National Library of Medicine, 2026); [Erythrocyte Sedimentation Rate (ESR): MedlinePlus Medical Test](https://medlineplus.gov/lab-tests/erythrocyte-sedimentation-rate-esr/) (MedlinePlus, US National Library of Medicine, 2026); [About Sepsis | Sepsis | CDC](https://www.cdc.gov/sepsis/about/index.html) (Centers for Disease Control and Prevention (CDC), 2026); [Association between site of infection and in-hospital mortality in patients with sepsis admitted to emergency departments of tertiary hospitals in Medellin, Colombia](https://europepmc.org/article/PMC/PMC6443304) (Revista Brasileira de terapia intensiva, 2019).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/systemic-effects-of-inflammation-fever-acute-phase-proteins-leukocytosis-sepsis/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/systemic-effects-of-inflammation-fever-acute-phase-proteins-leukocytosis-sepsis/