Fevers and Pyrogens

Art & Research: Erika Vallence

Further Reading Literature: Erika Vallence


The term pyrogen refers to any substance that causes a fever (NCBI). Pyrogens can be classified as being either exogenous or endogenous (NCBI). Exogenous pyrogens come from outside the body and can be bacteria, viruses, fungi, or even certain foreign non-microbial substances like drugs (NCBI).

Endogenous pyrogens are produced within the body and are usually cytokines that are activated at exposure to infectious substances, tissue injury, or even necrosis (NCBI).

Immune reaction to pyrogens

When immune cells come in contact with pyrogens, the immune cells will bind with specific toll-like receptors in order to recognize the specific substance they came in contact with (NCBI).

The immune response is fine-tuned to prevent both infections, from not reacting enough, and inflation, from reacting too much (NCBI).

Immune signaling

After the immune cells detect the pyrogen, reactions happening within the cell will cause cytokines to be released (NCBI). Cytokines are proteins, often produced by immune cells like monocytes, macrophages, and T cells, which regulate the immune response (NCBI). In our case, cytokines, like IL-1, play a role in inducing fever by stimulating the production of prostaglandin E ₂ (PEG2) (NCBI).

Prostaglandin E2

Prostaglandin E ₂ (PGE2) is the hormone that will be the key to causing a fever (Kita et al.). During the fever process, PGE2 binds to the receptor EP3 in order to have an effect on the hypothalamus (Kita et al.). PGE2 also plays a role in the nervous system’s response to stress and in smooth muscle regulation by binding to other receptors like EP1, EP2, and EP4 (Kita et al.).

PGE2 and fever

An increase of PGE2 in the hypothalamus signals the hypothalamus to raise the body’s thermostat or set point above the normal temperature range (96.8-99.6°F/36-37.6°C) to a fever temperature range (100.4-104°F/38-40°C) (Kita et al.). 

The hypothalamus will tell the body to produce heat through ways like shivering and to preserve heat through ways like constricting blood vessels (Kita et al.).

Fever reducers

Since fever reducers like aspirin, acetaminophen, and ibuprofen work by reducing PGE2 production in order to reduce the body’s set point, it is important to remember that these medications will have little use to treat hyperthermia or heatstroke since these conditions are unrelated to the body’s set point (Kita et al.). 

If you think someone is showing signs of heatstroke such as irrational behavior, shallow breathing, and a body temperature over 104°F, call 911 and try to bring them to a cooler environment.

Want to learn more about this topic?

Check out the additional resources below!