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Chapter 2 Innate and Adaptive Immunity: From Cell Defense to Tissue Repair

Section 5:  Fever

Zoë Soon

A rise in body temperature above 37.2°C is called a fever, caused by pyrogens released in response to cellular damage or irritation.  A low-grade fever (38-39°C) is a beneficial innate response – it accelerates WBC activity, inhibits pathogen metabolism and replication, and speeds healing.

Endogenous pyrogens Produced by WBCs (e.g., interferons and interleukins).

Stimulate the thermoregulation center in the hypothalamus to raise the body’s temperature set point.
Exogenous pyrogens Foreign components (e.g., LPS – lipopolysaccharides from bacterial cell walls) that also trigger fever.
The role of the hypothalamus in the inflammatory response, fever. The activation of leukocytes during an infection or injury can result in the release of endogenous pyrogens (e.g., a set of cytokines including specific interleukins) which trigger the production of prostaglandin E2 (PGE2) which resets the hypothalamus, the body's thermostat, to initiate fever. Gram-negative bacteria have lipopolysaccharide (LPS) capsule, which is considered an endotoxin and an exogenous pyrogen, which causes WBCs to produce more of these pyrogens. Some pathogen can lead to high levels of pyrogens being released which can cause dangerously high spiking fevers.
The role of the hypothalamus in the inflammatory response, fever. The activation of leukocytes during an infection or injury can result in the release of endogenous pyrogens (e.g., a set of cytokines including specific interleukins) which trigger the production of prostaglandin E2 (PGE2) which resets the hypothalamus, the body’s thermostat, to initiate fever. Gram-negative bacteria have lipopolysaccharide (LPS) capsule, which is considered an endotoxin and an exogenous pyrogen, which causes WBCs to produce more of these pyrogens. Some pathogens can lead to high levels of pyrogens being released which can cause dangerously high spiking fevers.

The Four Stages of Fever

1.  Prodromal Onset stage – beginning to feel unwell;  pyrogens start circulating
2.  Chills Pyrogens reset the hypothalamic thermostat to a higher level (e.g., 39°C).  Because the body is not yet at 39°C, you feel cold and shiver despite already being warm. 

The body raises temperature through shivering, erector pili muscle contraction (form goosebumps and generate heat), and increasing heart rate, and basal metabolic rate (BMR).   

Skin pallor as cutaneous vasoconstriction occurs to reduce heat loss.  

Behavioural changes (layering clothing, blankets) also occur.
3.  Flush Body temperature is at or above 37.2°C.  Remains in this stage as long as pyrogens continue stimulating the hypothalamus.
4.  Defervescence (Sweating) Infection resolves; pyrogens diminish; hypothalamus resets to 37°C.

The body cools by:  (a) vasodilating cutaneous vessels to radiate heat; (b) sweating; (c) reducing BMR and heart rate; (d) reducing movement; and (e) removing extra clothing and blankets.

High Fever and Its Dangers

A spiking fever of 40°C or above can cause febrile seizures (putting the brain at risk for neural damage) and is also characteristic of heat stroke (inability to thermoregulate and cool the body).

Febrile seizure treatment involves placing the child on a soft flat surface away from sharp objects, while keeping mouth clear of objects and timing the seizure’s duration.

Both febrile seizures and heat stroke can quickly evolve to become medical emergencies and should involve calling 9-1-1.

Heat stroke treatment should involve cooling the person as quickly as possible by moving them to a cooler area, and using cold water and ice packs, as well as providing cool water to drink.

A blunted or absent febrile response in the elderly or immunosuppressed may delay diagnosis and treatment, making clinical assessment more challenging.

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