Why Do We Get a Fever? The Body Turning Up Its Own Thermostat

Body temperature is held near 37 degrees by a region of the hypothalamus that compares the blood's temperature with a set point and orders heat to be made or lost accordingly: shivering, constricted skin vessels and a search for blankets when the body is below the set point; sweating, flushed skin and thrown-off covers when it is above. A fever moves the set point. Once the thermostat is set to 39, a body at 37 is two degrees too cold, and the patient shivers and feels chilled while their temperature climbs; when the infection subsides and the set point drops back, the body is suddenly too hot, and the fever breaks in a sweat. The chills at the start and the sweat at the end are the same machinery running in opposite directions.

The signal is inflammatory. When immune cells meet bacteria, viruses or damaged tissue they release messenger proteins, cytokines such as interleukin-1 and interleukin-6, which travel in the blood to the brain and cause the lining of its vessels to make prostaglandin E2, a small fat molecule that acts on the hypothalamus and raises the set point. Aspirin, ibuprofen and paracetamol all lower fever by blocking the enzyme that makes that prostaglandin, which is why they work on the symptom without touching the infection. The sequence:

• •Infection or injury activates immune cells
• •They release cytokines into the blood
• •The cytokines reach the brain and trigger prostaglandin E2
• •The hypothalamus raises the set point
• •The body shivers, conserves heat and warms up to match
• •When the cytokines fall, the set point returns and the body sweats down

The benefit works on both sides of the fight. Many bacteria grow best at 37 degrees and slowly at 39 or 40, and a fever also lowers the iron available in the blood, which bacteria need. The immune system meanwhile runs faster: white blood cells move more quickly, produce more antibodies and kill more effectively at fever temperatures, and the heat-shock proteins that cells make when warm help present the invader to the immune system. The evidence that this matters is direct. Cold-blooded animals, which cannot heat themselves, seek warmth when infected and die at higher rates if prevented; rabbits given bacteria survive more often if allowed to run a fever; and in several studies of humans with severe infections, those given drugs to suppress fever fared no better, and sometimes slightly worse, than those left alone, though the differences are small.

A fever costs energy, about ten percent more per degree, which a well-nourished adult can afford and a frail one may not, and it is unpleasant. Above about 41 degrees, which infection rarely produces, proteins begin to be damaged and the risk of harm is real, but such temperatures usually come from heatstroke, drugs or brain injury, where the thermostat itself is broken, rather than from a fever, which the hypothalamus caps. The febrile convulsions of small children, which affect about one in thirty and terrify parents, are caused by the speed of the rise rather than its height, do not cause lasting harm, and are not prevented by paracetamol. The modern advice, which reversed the habit of a century, is to treat the discomfort rather than the number: give an antipyretic if the patient is miserable, not because the thermometer says 38.5, and let a fever run if the person is coping.

A fever without an obvious cause that lasts more than a few weeks is a diagnosis in its own right, and its causes range across hidden infections, cancers such as lymphoma and inflammatory diseases. Some fevers come in patterns: the every-other-day or every-third-day cycles of malaria, timed to the parasite bursting out of red cells, were how physicians told the types apart before microscopes. And some people cannot make one: the very old, the newborn and those on high-dose steroids or chemotherapy may have a serious infection with a normal or low temperature, which is why in those groups the absence of fever is not reassurance.

A fever is the hypothalamus raising the body's temperature set point in response to cytokines released by immune cells, so that the patient shivers up to the new level and sweats back down when it falls. The higher temperature slows many microbes and speeds the immune response, which is why the reaction has been conserved across the animal kingdom; it is rarely dangerous in itself, and the current advice is to treat the discomfort rather than the number.