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  1. Which region of the brain is primarily responsible for temperature regulation?

  2. Does core temperature vary at different times of the day?

  3. Is fever beneficial?

  4. How and when should fever be treated?

  5. How do acetylsalicylic acid (ASA or aspirin) and acetaminophen act to reduce fever?


Body temperature is regulated by the hypothalamus in combination with many other neural structures, including the brain stem, spinal cord, and sympathetic ganglia. The region of the hypothalamus near the optic chiasm is thought to be primarily responsible for maintaining the body’s core temperature. A distinct temperature set point is established, and when the body’s core temperature drops below that set point, the nervous system increases body metabolism and stimulates shivering and chills. When core temperature exceeds that set point, the nervous system increases peripheral blood flow and sweating occurs. “Normal” body temperature is 37°C, but it varies from individual to individual, following a normal distribution. Some individuals therefore have a lower set point, and others have a higher set point than the mean “normal” temperature. Furthermore, each individual’s core temperature varies during the day, being lower in the morning and increasing in the evening. Before deciding that a patient has a fever, the physician must be familiar with that patient’s normal set point and diurnal core temperature variation.


Fever is a consequence of the hypothalamus responding to inflammatory mediators. Among the mediators thought to stimulate a rise in the normal core temperature set point are interleukin 1 (IL-1), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interferon γ (IFN-γ). These cytokines are released primarily by monocytes, macrophages, and endothelial cells in response to invasion by various pathogens and by other inflammatory stimuli. Investigators speculate that these cytokines stimulate the circumventricular organs near the optic chiasm, activating phospholipase A2, which in turn stimulates the cyclooxygenase pathway to produce increased levels of prostaglandin E2. This small molecule crosses the blood–brain barrier and stimulates the neurons within the hypothalamus and brain stem responsible for thermal regulation.


In addition to serving as a warning sign for the onset of infection, fever is thought to be beneficial. The growth of some viruses, bacteria, fungi, and parasites are inhibited by a rise in temperature above 37°C. Fever has also been shown to enhance the ability of macrophages and neutrophils to kill foreign pathogens and to improve cell-mediated immune function.

Depending on the individual patient, fever may also have harmful effects. Patients with heart disease may suffer cardiac ischemia because of the increase in heart rate and the oxygen demands associated with fever. Each one degree increase in temperature above 37°C is accompanied by a 13% increase in O2 consumption. Patients with severe pulmonary disease ...

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