Fever Facts: Causes, and Treatments

By: Ruchi Chaube Ph.D.
Just like how a thermostat regulates room temperature, the hypothalamus, an almond shaped organ located at the base of the brain, regulates body temperature.
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The Hypothalamus responds to stimuli, both external and internal, and adjusts the body temperature to the core setting of 98.6º F.

The body temperature changes during the day; mornings: 97º F & evenings: 99º F.

The temperature can also vary depending on part of the body that is being measured; rectum (99.5º F to 100.9º F), oral (99.9º F) & ear (95.7º F to 100.0º F).

The above values serve as Threshold and any deviations trigger the hypothalamus to adjust the temperature through heat loss or gain.

If left untreated, high body temperature or fever (100.4º F or higher) can prove fatal.

The metabolic processes in the body work optimally at the core temperature. Higher body temperature that sustains over a period of time can negatively affect or completely block these metabolic processes.

  1. Causes and symptoms of fever:

Fever is caused by the invading foreign entities called pyrogens (bacteria, viruses, drugs or toxins).

The body’s natural defense against these pyrogens activates the immune system that responds by raising the body’s temperature. The bacteria and viruses cannot survive at high temperature.

However, as a result of high temperature the body also suffers from the symptoms of unease including:

  • Feeling cold
  • Shivering
  • Lack of appetite
  • Dehydration
  • Body pain
  • Lethargy
  • Sleepiness
  • Sweating

Fevers at 104º F or above can also cause confusion, delirium, and convulsions.

  1. Body’s response to fever:

When a pyrogen infects the body, the ‘first responders’ to the site of infection are the immune cells called macrophages. Macrophages ingest the pyrogens and destroy them.

How do Macrophages work?

Macrophages are cells that internalize the pyrogens through the surface receptors called Toll-like receptors and produce cytokines that are released into the bloodstream to kill the pyrogen.

Of the many cytokines released in the blood, IL-6 is taken up by the endothelial cells lining the blood vessels of the brain and stimulates the enzymes cyclooxygenase 1 and 2 (COX 1 and 2) to produce prostaglandin E2 (PGE2). PGE2 released from the endothelial cells cross the blood-brain barrier and inactivates the warm sensitive neurons (WSNs) in the preoptic area (POA) of the hypothalamus. As a result of this, the WSNs lose their ability to sense warmth. The hypothalamus, therefore, assumes that there is a drop in the core temperature and start processes that lead to heat production (thermogenesis) in the body like activation of the sympathetic nervous system to release noradrenaline from the adrenal gland. Noradrenaline initiates burning of fats (metabolism) and causes vasoconstriction in the muscles, which brings shivering in the body.

When fever sustains for a longer time, hypothalamus triggers the blood vessels beneath the skin to swell or dilate to allow warm blood to flow near the surface of the skin and release heat in the form of sweat.

Why do you sweat when you have fever?

A study published in Science (DOI: 10.1126/science.aaf7537) reported that sustained fever can induce heat stress in the body which produce molecules called reactive oxygen species (ROS). The ROS activate the ion channel, TRPM2, expressed in a subset of WSNs in the POA of the hypothalamus which in turn activate these neurons. The activated WSNs extend to the paraventricular nucleus of the hypothalamus that sends the signals to turn on the parasympathetic nervous system to release hormones such as adrenaline and corticosterone from the adrenal gland. Adrenaline dilates the blood vessels that releases heat from the skin (sweating), and corticosterone inhibits thermogenesis brought by the burning of the fats.

In contrast, when we are cold, the blood vessels near the skin narrow or constrict pulling the hairs on the skin upright to reduce heat loss (goose bumps). The hairs in the upright position trap warmth. The heat loss is also prevented by the constriction of the muscles attached to the skeleton which brings shivering in the body.


  1. Prevention and treatments of fever:

The most commonly used drugs to treat fever are acetaminophen (paracetamol) and the non-steroidal anti-inflammatory drugs like ibuprofen and aspirin.

Paracetamol has stronger antipyretic and analgesic effect, but less anti-inflammation effect.

Anti-inflammatory drugs have an analgesic, antipyretic, and anti-inflammation effect. As a side effect, these drugs can result in suppression of inflammation of the gut which serves as a protective layer against bacteria and other foreign entities entering the gut with the ingested food. And, when taken for a long time or at high doses, these drugs can cause diarrhea, vomiting, gut ulceration and bleeding. Aspirin is not recommended for children and can cause Reye’s syndrome (swelling of liver and brain).

For temporary relief you can use therapies like lukewarm or cold wraps, bath, wet cloth on forehead, and fanning.

These therapies work through the thermoreceptors present in the skin. These are the sensory neurons which sense coldness in the surroundings and send the signal to the hypothalamus to adapt to the new temperature by lowering it and thus reducing the fever.

These therapies do not treat the cause of the fever, but if you have high fever these can be used along with the medication to maximize relief. 

This article, and the products mentioned are not intended to diagnose, treat, cure, or prevent any disease. Please see your health care provider before taking any supplements or starting a new program.

Ruchi Chaube is a Freelance Medical Writer and a regular science blogger. She holds a Ph.D. in Biochemistry and has worked as a biomedical postdoctoral scientist at Case Western Reserve University, USA, and currently works at McMaster University, Canada. She is a member of the American Medical Writers Association (AMWA) and contributes in medical writing tasks in AMWA and the AMWA-Canada chapter.

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