What causes pyrexia? An expert guide to fever triggers

September 24, 2025 •

4 min read

A startling statistic reveals that elevated body temperature, or pyrexia, is one of the most frequently detected abnormal signs in patients across different healthcare settings. Understanding what causes pyrexia is key to identifying its underlying trigger and ensuring proper care.

Quick Summary

Pyrexia, or fever, is caused by fever-inducing substances called pyrogens, which elevate the body's thermoregulatory set-point in the brain. These pyrogens can originate from various sources, including infectious agents, inflammatory conditions, and certain medications, signaling an immune response.

Key Points

Pyrogens Trigger Pyrexia: Fever is primarily caused by substances called pyrogens, which can come from infectious agents (exogenous) or the body's immune cells (endogenous).
Hypothalamus Sets the Temperature: Pyrogens raise the body's temperature set-point in the hypothalamus, the brain's thermostat, which causes the body to increase its core temperature.
Many Causes Exist: Causes range from common infections (viral, bacterial) to inflammatory conditions, autoimmune diseases, and even cancer.
Medications Can Cause Fever: Some medications, including certain antibiotics, can induce a drug-induced fever as a side effect.
Pyrexia is Not Hyperthermia: Unlike pyrexia, hyperthermia involves an uncontrolled rise in body temperature without a change in the hypothalamic set-point and does not respond to fever-reducing medication.
Warning Signs Require Care: Certain symptoms accompanying a fever, like a stiff neck, confusion, or rash, warrant immediate medical attention.

The Core Mechanism Behind a Fever

Pyrexia, the medical term for fever, is a physiological response orchestrated by the body's immune system to combat perceived threats. At its core, pyrexia is triggered by substances known as pyrogens, which influence the hypothalamus, the brain's temperature control center. The hypothalamus resets the body's temperature set-point upward, leading to an increase in core body temperature. The body then initiates heat-producing behaviors, such as shivering and vasoconstriction (constriction of blood vessels), to raise the body's temperature to this new, higher set-point.

There are two main types of pyrogens:

Exogenous Pyrogens: These originate from outside the body, primarily from infectious agents like bacteria, viruses, fungi, and parasites. A common example is the endotoxins produced by Gram-negative bacteria.
Endogenous Pyrogens: These are produced by the body's own immune cells in response to an infection or inflammation. Examples include cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha).

Why a Fever is a Defense Mechanism

While uncomfortable, a fever is a powerful evolutionary defense. An elevated temperature makes the body a less hospitable environment for many pathogens, slowing their multiplication and replication. It also enhances the immune system's function by increasing the activity and mobility of white blood cells and stimulating the production of interferons, which fight viral infections.

Infectious Causes of Pyrexia

Infections are the most common cause of pyrexia. When pathogens invade the body, they trigger an immune response that leads to a fever.

Viral Infections

Respiratory viruses: The common cold, influenza (flu), and COVID-19 are frequent culprits.
Gastrointestinal viruses: Viral gastroenteritis, which causes vomiting and diarrhea, is another common cause.
Childhood illnesses: Viruses like chickenpox and measles can cause fever, though many are preventable with vaccines.

Bacterial Infections

Respiratory infections: Strep throat, bacterial pneumonia, and sinusitis can lead to fever.
Urinary tract infections (UTIs): Infections in the urinary system often present with fever.
Skin infections: Conditions like cellulitis can cause a localized fever and inflammation.
Sepsis: A severe and life-threatening response to an infection can cause a high fever and is a leading cause of pyrexia in hospitalized patients.

Other Pathogens

Parasites: Diseases like malaria cause characteristic fever patterns.
Fungal infections: Fungal pathogens can also trigger a febrile response.

Non-Infectious Triggers for Pyrexia

Infections aren't the only source of pyrexia. Other conditions can also induce a febrile state by releasing endogenous pyrogens.

Inflammatory and Autoimmune Disorders

Rheumatoid Arthritis & Lupus: These autoimmune diseases cause the immune system to mistakenly attack healthy tissue, leading to chronic inflammation and fever.
Inflammatory Bowel Disease (IBD): Crohn's disease and ulcerative colitis can cause systemic inflammation and fever.
Vasculitis: The inflammation of blood vessels can result in a fever.

Malignancies

Certain cancers, such as Hodgkin's disease, leukemia, and lymphomas, can cause a fever as a primary symptom. Cancerous cells themselves or the body's reaction to them can produce pyrogens.

Drug-Induced Fever

Medications: Some drugs can cause a fever as a side effect. Common examples include certain antibiotics, antihistamines, and seizure medicines. This is a diagnosis of exclusion, meaning other causes must be ruled out first.

Post-Vaccination Fever

Some vaccines are designed to elicit an immune response by introducing weakened or inactive pathogens. A low-grade fever after a vaccination is a normal sign that the body is building immunity.

Neurological and Other Causes

In some cases, the cause of pyrexia is directly related to the central nervous system or other internal issues.

Neurogenic Fever

CNS Damage: Damage to the hypothalamus from trauma, intracerebral bleeding, or increased intracranial pressure can disrupt temperature regulation, causing a high fever that is often resistant to antipyretic medications.

Blood Clots

Thrombophlebitis: The presence of a blood clot can cause a fever, particularly if it leads to inflammation.

Pyrexia vs. Hyperthermia: A Critical Distinction

It's crucial to differentiate between pyrexia (fever) and hyperthermia, as they have different causes, mechanisms, and treatments.


Feature	Pyrexia (Fever)	Hyperthermia
Mechanism	Hypothalamus increases the body's temperature set-point.	The set-point is unchanged; the body's temperature rises uncontrollably.
Cause	Primarily infectious, inflammatory, or malignant triggers.	Excessive heat exposure or unregulated heat production.
Thermoregulation	Body maintains a controlled increase in temperature through shivering and vasoconstriction.	Body's temperature-regulating system is overwhelmed or impaired, and heat cannot be dissipated.
Treatment Response	Responds to antipyretic medications (fever reducers).	Does not respond to antipyretic medications. Requires external cooling.
Example Causes	Flu, strep throat, lupus, cancer.	Heatstroke, certain drug reactions (e.g., neuroleptic malignant syndrome).

When to Seek Medical Attention

While many fevers are self-limiting, it is essential to be aware of certain signs that may indicate a serious underlying condition. You should contact a healthcare provider for a fever that is very high (above 103°F in adults), persistent, or accompanied by other severe symptoms. Specific signs requiring immediate medical attention include:

Severe headache
Stiff neck or neck pain
Difficulty breathing or chest pain
Mental confusion or unusual behavior
Persistent vomiting
Rash or unusual sensitivity to bright light
Pain when urinating
Seizures

Infants under 3 months with a rectal temperature of 100.4°F or higher require immediate medical evaluation. For more information on fever in adults, refer to resources from organizations like the National Institutes of Health.

Conclusion

Pyrexia is a common symptom with a complex network of underlying causes, ranging from routine viral infections to more serious conditions like autoimmune diseases and malignancies. The body's ability to trigger a fever is a sophisticated immune response, but it can also be a sign of a critical issue. By understanding the intricate mechanisms and various triggers, individuals can make informed decisions about when to manage a fever at home and when to seek professional medical help for a proper diagnosis and treatment of the root cause.

Frequently Asked Questions

The primary difference lies in the body's thermoregulatory set-point. In pyrexia (fever), the hypothalamus raises the set-point to a higher temperature. In hyperthermia, the set-point remains normal, but the body's temperature rises uncontrollably due to external factors or unregulated heat production.

Yes, some medications can cause a fever as a side effect. This is known as drug-induced fever and can be triggered by certain antibiotics, antihistamines, and seizure medicines, among others.

The body raises its temperature during pyrexia to create an unfavorable environment for many pathogens, which cannot thrive at higher temperatures. It also boosts the activity of immune cells and production of infection-fighting agents like interferons.

Not necessarily. A low-grade fever is often a sign that your immune system is working effectively to fight off an infection. In many cases, it does not require treatment with medication unless it causes significant discomfort.

You should seek medical help if a fever is very high (above 103°F in adults), lasts for more than a few days, or is accompanied by severe symptoms like a stiff neck, persistent vomiting, confusion, or difficulty breathing.

Yes, autoimmune and inflammatory disorders can cause pyrexia. Conditions such as rheumatoid arthritis, lupus, and inflammatory bowel disease can trigger a febrile response as part of the body's systemic inflammation.

Pyrogens are fever-inducing substances that cause the hypothalamus to raise the body's temperature set-point. They can be exogenous (from external sources like bacteria) or endogenous (produced by the body's immune system).