A fever is an elevation of the body’s core temperature above the normal range of approximately 37 degrees Celsius (98.6 degrees Fahrenheit). This rise is not a sign of malfunction, but a deliberate response orchestrated by the immune system. When the body encounters an infectious threat, it intentionally raises its internal thermal setting. This creates an environment less hospitable to invaders and sets the stage for a more effective fight against the pathogen.
Setting the Temperature Higher: The Role of Pyrogens
The process of generating a fever begins with the body recognizing foreign or harmful material, known collectively as pyrogens. Pyrogens can be exogenous, originating outside the body, such as lipopolysaccharide on bacterial cell walls. They can also be endogenous, released from the host’s own immune cells, like macrophages, after detecting a threat.
Once activated, immune cells release signaling molecules, specifically cytokines (Interleukin-1 and Interleukin-6), which act as internal pyrogens. These endogenous pyrogens travel through the bloodstream to the hypothalamus, the brain area functioning as the body’s thermostat. This signaling causes the hypothalamus to synthesize Prostaglandin E2 (PGE2).
PGE2 is the final mediator that resets the hypothalamic temperature set point upward. The body then perceives its current temperature as too low relative to this new, higher set point. To reach the elevated temperature, the body triggers heat-generating and heat-conserving mechanisms. This includes peripheral vasoconstriction to reduce heat loss, and muscle contractions that manifest as shivering or chills to actively generate warmth.
How Elevated Heat Hinders Pathogens
The elevated thermal set point serves two purposes: directly inhibiting the pathogen and enhancing the body’s defense mechanisms. Many infectious agents, including bacteria and viruses, are temperature-sensitive and thrive best at 37 degrees Celsius. Raising the temperature even a few degrees creates a thermal restriction zone that significantly impairs the pathogen’s ability to replicate and survive.
This heat also aids the immune response by enhancing specialized immune cell function. Fever-range temperatures, such as 39 degrees Celsius, boost the proliferation and cytokine production of T helper cells. This thermal boost also increases the phagocytic capacity of monocytes and macrophages, making them more effective at engulfing and destroying microbial invaders.
The heat promotes the movement of lymphocytes, integral to adaptive immunity, to the site of infection. This is facilitated by the increased expression of Heat Shock Protein 90 (Hsp90), which enhances the activation of integrins on T lymphocytes, allowing them to migrate more efficiently into infected tissues. Simultaneously, the cytokines that trigger the fever stimulate the liver to increase the production of acute phase proteins, such as C-reactive protein. These proteins act as opsonins, coating pathogens and marking them for destruction by phagocytes, accelerating the overall defense strategy.
Monitoring Fever: When the Immune Response Becomes Risky
While fever demonstrates a functioning immune system, temperature regulation can become dangerous if the heat is excessive or uncontrolled. It is important to distinguish between a controlled fever, where the hypothalamic set point is raised, and hyperthermia. Hyperthermia is an unregulated rise in body temperature, often caused by external factors like heatstroke or certain drugs. Hyperthermia is an emergency because cooling mechanisms fail to compensate, allowing the temperature to climb dangerously high, often exceeding 41 degrees Celsius (105.8 degrees Fahrenheit).
A prolonged or extremely high temperature, particularly above 40 degrees Celsius (104 degrees Fahrenheit), can threaten cells by causing protein denaturation and neurological damage. Medical guidance suggests seeking professional care for any fever in an infant under three months old, due to immature immune systems, or for any fever lasting more than three to five days in older children and adults. Concerning symptoms like confusion, severe headache, or difficulty breathing, regardless of the temperature, warrant immediate medical attention.
Fever-reducing medications, such as acetaminophen or ibuprofen, work by blocking the synthesis of Prostaglandin E2, resetting the hypothalamus to a lower temperature set point. The primary purpose of these medications is to provide comfort, reduce metabolic stress, and mitigate the risk of excessively high temperatures.
Since fever plays a beneficial role, many professionals advise against the routine use of fever reducers for low-grade fevers. They recommend use only when the fever causes significant discomfort or approaches a risky threshold.